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1.
Clin Transl Gastroenterol ; 15(6): e1, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38986526

RESUMO

INTRODUCTION: Diet can affect ammoniagenesis in cirrhosis and hepatic encephalopathy (HE), but the impact of dietary preferences on metabolomics in cirrhosis is unclear. As most Western populations follow meat-based diets, we aimed to determine the impact of substituting a single meat-based meal with an equal protein-containing vegan/vegetarian alternative on ammonia and metabolomics in outpatients with cirrhosis on a meat-based diet. METHODS: Outpatients with cirrhosis with and without prior HE on a stable Western meat-based diet were randomized 1:1:1 into 3 groups. Patients were given a burger with 20 g protein of meat, vegan, or vegetarian. Blood for metabolomics via liquid chromatography-mass spectrometry and ammonia was drawn at baseline and hourly for 3 hours after meal while patients under observation. Stool microbiome characteristics, changes in ammonia, and metabolomics were compared between/within groups. RESULTS: Stool microbiome composition was similar at baseline. Serum ammonia increased from baseline in the meat group but not the vegetarian or vegan group. Metabolites of branched chain and acylcarnitines decreased in the meat group compared with the non-meat groups. Alterations in lipid profile (higher sphingomyelins and lower lysophospholipids) were noted in the meat group when compared with the vegan and vegetarian groups. DISCUSSION: Substitution of a single meat-based meal with a non-meat alternatives results in lower ammoniagenesis and altered serum metabolomics centered on branched-chain amino acids, acylcarnitines, lysophospholipids, and sphingomyelins in patients with cirrhosis regardless of HE or stool microbiome. Intermittent meat substitution with vegan or vegetarian alternatives could be helpful in reducing ammonia generation in cirrhosis.


Assuntos
Amônia , Dieta Vegana , Dieta Vegetariana , Fezes , Microbioma Gastrointestinal , Encefalopatia Hepática , Cirrose Hepática , Metabolômica , Humanos , Amônia/sangue , Amônia/metabolismo , Cirrose Hepática/dietoterapia , Cirrose Hepática/metabolismo , Cirrose Hepática/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Encefalopatia Hepática/dietoterapia , Encefalopatia Hepática/sangue , Encefalopatia Hepática/etiologia , Fezes/química , Fezes/microbiologia , Idoso , Carnitina/análogos & derivados , Carnitina/sangue , Carnitina/metabolismo , Carne , Aminoácidos de Cadeia Ramificada/sangue , Aminoácidos de Cadeia Ramificada/metabolismo , Adulto
2.
Am J Gastroenterol ; 119(5): 977-981, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-39008900

RESUMO

Lactulose-based hepatic encephalopathy treatment requires bowel movements/day titration, which is improved with Bristol stool scale (BSS) incorporation. Dieta app evaluates artificial intelligence (AI)-based BSS (AI-BSS) with stool images. Initially, controls (N = 13) and cirrhosis patients on lactulose/not on lactulose (n = 33) were trained on the app. They entered self-reported BSS (self-BSS) with AI-BSS communicated. Lactulose dose changes were tracked. A subset (n = 12) was retested with AI communication blocked. Most subjects were comfortable with the app. Self/AI-BSS and lactulose dose/AI-BSS correlation increased with app use. AI-BSS communications improved insight into self-BSS over time. Dieta app to gauge stool AI characteristics was acceptable and increased insight into lactulose dose and BSS in cirrhosis.


Assuntos
Inteligência Artificial , Fezes , Fármacos Gastrointestinais , Encefalopatia Hepática , Lactulose , Aplicativos Móveis , Smartphone , Humanos , Encefalopatia Hepática/terapia , Lactulose/uso terapêutico , Lactulose/administração & dosagem , Masculino , Feminino , Fezes/química , Pessoa de Meia-Idade , Fármacos Gastrointestinais/uso terapêutico , Fármacos Gastrointestinais/administração & dosagem , Idoso , Cirrose Hepática/complicações , Adulto
4.
Int J Part Ther ; 12: 100015, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38827121

RESUMO

Purpose: To report clinical and dosimetric characteristics of 5-fraction stereotactic ablative radiotherapy (SABR) using intensity modulated proton therapy (IMPT) for localized prostate cancer. Materials and Methods: All patients receiving IMPT SABR from 2017 to 2021 for localized prostate cancer at our institution were included. Five fractions were delivered every other day to the prostate +/- seminal vesicles [clinical target volume (CTV)] with 3 mm/3% robustness. A 4-field arrangement with 2 anterior oblique and 2 opposed lateral beams was used in most patients (97%), and most (99%) had a retroprostatic hydrogel spacer. Results: A total of 534 patients with low (14%), favorable intermediate (45%), unfavorable intermediate (36%), high (4.0%), or very high-risk (0.6%) disease are evaluated. Prescription dose was 36.25 Gy (31%), 38 Gy (38%), or 40 Gy (31%) was prescribed. Median volume percentage of CTV receiving at least 100% of prescription dose [V100% (%)] was 100% [interquartile range: 99.99-100]. Rectum V50% (%), V80% (%), and V90% (%) were significantly lower in patients who had spacer, with a mean difference of -9.70%, -6.59%, and -4.42%, respectively, compared to those who did not have spacer. Femoral head dose was lower with a 4-field arrangement. Mean differences in left and right femoral head V40% (%) were -6.99% and -10.74%, respectively. Conclusion: We provide a large, novel report of patients treated with IMPT SABR for localized prostate cancer. Four-field IMPT with hydrogel spacer provides significant sparing of rectum and femoral heads without compromising target coverage.

5.
Cancers (Basel) ; 16(11)2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38893199

RESUMO

Prostate cancer lung metastasis represents a clinical conundrum due to its implications for advanced disease progression and the complexities it introduces in treatment planning. As the disease progresses to distant sites such as the lung, the clinical management becomes increasingly intricate, requiring tailored therapeutic strategies to address the unique characteristics of metastatic lesions. This review seeks to synthesize the current state of knowledge surrounding prostate cancer metastasis to the lung, shedding light on the diverse array of clinical presentations encountered, ranging from subtle radiological findings to overt symptomatic manifestations. By examining the diagnostic modalities utilized in identifying this metastasis, including advanced imaging techniques and histopathological analyses, this review aims to provide insights into the diagnostic landscape and the challenges associated with accurately characterizing lung metastatic lesions in prostate cancer patients. Moreover, this review delves into the nuances of therapeutic interventions employed in managing prostate cancer lung metastasis, encompassing systemic treatments such as hormonal therapies and chemotherapy, as well as metastasis-directed therapies including surgery and radiotherapy.

6.
Clin Transl Gastroenterol ; 15(6): e1, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38696431

RESUMO

INTRODUCTION: Diet can affect ammoniagenesis in cirrhosis and hepatic encephalopathy (HE), but the impact of dietary preferences on metabolomics in cirrhosis is unclear. As most Western populations follow meat-based diets, we aimed to determine the impact of substituting a single meat-based meal with an equal protein-containing vegan/vegetarian alternative on ammonia and metabolomics in outpatients with cirrhosis on a meat-based diet. METHODS: Outpatients with cirrhosis with and without prior HE on a stable Western meat-based diet were randomized 1:1:1 into 3 groups. Patients were given a burger with 20 g protein of meat, vegan, or vegetarian. Blood for metabolomics via liquid chromatography-mass spectrometry and ammonia was drawn at baseline and hourly for 3 hours after meal while patients under observation. Stool microbiome characteristics, changes in ammonia, and metabolomics were compared between/within groups. RESULTS: Stool microbiome composition was similar at baseline. Serum ammonia increased from baseline in the meat group but not the vegetarian or vegan group. Metabolites of branched chain and acylcarnitines decreased in the meat group compared with the non-meat groups. Alterations in lipid profile (higher sphingomyelins and lower lysophospholipids) were noted in the meat group when compared with the vegan and vegetarian groups. DISCUSSION: Substitution of a single meat-based meal with a non-meat alternatives results in lower ammoniagenesis and altered serum metabolomics centered on branched-chain amino acids, acylcarnitines, lysophospholipids, and sphingomyelins in patients with cirrhosis regardless of HE or stool microbiome. Intermittent meat substitution with vegan or vegetarian alternatives could be helpful in reducing ammonia generation in cirrhosis.


Assuntos
Amônia , Dieta Vegana , Dieta Vegetariana , Fezes , Microbioma Gastrointestinal , Encefalopatia Hepática , Cirrose Hepática , Metabolômica , Humanos , Amônia/sangue , Amônia/metabolismo , Cirrose Hepática/dietoterapia , Cirrose Hepática/metabolismo , Cirrose Hepática/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Encefalopatia Hepática/dietoterapia , Encefalopatia Hepática/sangue , Encefalopatia Hepática/etiologia , Fezes/química , Fezes/microbiologia , Idoso , Carnitina/análogos & derivados , Carnitina/sangue , Carnitina/metabolismo , Carne , Aminoácidos de Cadeia Ramificada/sangue , Aminoácidos de Cadeia Ramificada/metabolismo , Adulto
7.
Am J Hum Genet ; 111(6): 1061-1083, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38723632

RESUMO

To identify credible causal risk variants (CCVs) associated with different histotypes of epithelial ovarian cancer (EOC), we performed genome-wide association analysis for 470,825 genotyped and 10,163,797 imputed SNPs in 25,981 EOC cases and 105,724 controls of European origin. We identified five histotype-specific EOC risk regions (p value <5 × 10-8) and confirmed previously reported associations for 27 risk regions. Conditional analyses identified an additional 11 signals independent of the primary signal at six risk regions (p value <10-5). Fine mapping identified 4,008 CCVs in these regions, of which 1,452 CCVs were located in ovarian cancer-related chromatin marks with significant enrichment in active enhancers, active promoters, and active regions for CCVs from each EOC histotype. Transcriptome-wide association and colocalization analyses across histotypes using tissue-specific and cross-tissue datasets identified 86 candidate susceptibility genes in known EOC risk regions and 32 genes in 23 additional genomic regions that may represent novel EOC risk loci (false discovery rate <0.05). Finally, by integrating genome-wide HiChIP interactome analysis with transcriptome-wide association study (TWAS), variant effect predictor, transcription factor ChIP-seq, and motifbreakR data, we identified candidate gene-CCV interactions at each locus. This included risk loci where TWAS identified one or more candidate susceptibility genes (e.g., HOXD-AS2, HOXD8, and HOXD3 at 2q31) and other loci where no candidate gene was identified (e.g., MYC and PVT1 at 8q24) by TWAS. In summary, this study describes a functional framework and provides a greater understanding of the biological significance of risk alleles and candidate gene targets at EOC susceptibility loci identified by a genome-wide association study.


Assuntos
Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Neoplasias Ovarianas , Polimorfismo de Nucleotídeo Único , Humanos , Feminino , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Carcinoma Epitelial do Ovário/genética , Transcriptoma , Fatores de Risco , Genômica/métodos , Estudos de Casos e Controles , Multiômica
8.
J Biomech ; 169: 112146, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38749240

RESUMO

Chiari Malformation (Chiari) is a congenital condition occurring from an inferior herniation of the cerebellar tonsils into the foramen magnum. Given the role of the cerebellum in postural control, it is reasonable to expect joint motion to be affected in this patient population. In fact, joint stiffness is a common self-reported symptom of Chiari, however it has never been assessed in these individuals. This study aimed to examine if ankle joint quasi-stiffness is correlated with Chiari severity. The human body was considered as an inverted oscillating pendulum without damping. A Fast Fourier Transform was used to extract natural frequency from the center of pressure trajectories during upright standing. Ankle joint quasi-stiffness was then calculated using the relationship between natural frequency and moment of inertia. Twelve Chiari participants (Chiari), six with decompression surgery (Chiari-D) and six without (Chiari-ND), and eight control individuals (Control) participated. Participants completed three, 30-second quiet standing trials on a force plate, focused on a target three meters in front of them. Chiari, regardless of surgery, had significantly lower quasi-stiffness than controls (Chiari-D vs. Control p = 0.0011, Chiari-ND vs. Control, p < 0.001). The proposed method is advantageous as it incorporates the entire center of pressure signal, minimizes error from instantaneous muscular dynamics, and does not require motion capture.


Assuntos
Articulação do Tornozelo , Malformação de Arnold-Chiari , Humanos , Malformação de Arnold-Chiari/fisiopatologia , Feminino , Adulto , Masculino , Articulação do Tornozelo/fisiopatologia , Posição Ortostática , Fenômenos Biomecânicos , Pessoa de Meia-Idade
9.
Sci Rep ; 14(1): 12446, 2024 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-38816557

RESUMO

Thoroughbred stallions that carry a double-homozygous genotype A/A-A/A for SNPs rs397316122 and rs69101140 in exon 5 of the FKBP6 gene (chr13; EquCab3.0) are uniquely subfertile due to impaired acrosomal exocytosis (IAE). In this study, the sperm proteome in frozen/thawed semen from subfertile Thoroughbred stallions was studied and compared to that of frozen/thawed sperm from fertile Thoroughbred stallions. A total of 2,220 proteins was identified, of which 140 proteins were found to be differentially abundant in sperm from the subfertile stallions compared to that of fertile stallions (83 less and 57 more abundant). Proteins of differential abundance in sperm from the subfertile stallions were mainly overrepresented in the "metabolism" and the "metabolism of lipids" pathways. One of these proteins, arylsulfatase F (ARSF), was studied by immunofluorescence. A lower proportion of sperm displaying ARSF signal at the acrosome region was observed in sperm from subfertile Thoroughbred stallions. In addition, heterologous zona pellucida binding assays revealed that sperm from subfertile Thoroughbred stallions bound at a lower proportion to zonae pellucidae than sperm from fertile Thoroughbred stallions. In conclusion, a group of differential abundance proteins, including some of acrosome origin, were identified in sperm from subfertile stallions with acrosome dysfunction.


Assuntos
Reação Acrossômica , Proteômica , Espermatozoides , Animais , Masculino , Cavalos , Proteômica/métodos , Espermatozoides/metabolismo , Exocitose , Acrossomo/metabolismo , Infertilidade Masculina/metabolismo , Infertilidade Masculina/veterinária , Infertilidade Masculina/genética , Proteoma/metabolismo , Fertilidade/genética , Zona Pelúcida/metabolismo
10.
Mol Ther Methods Clin Dev ; 32(1): 101208, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38414825

RESUMO

Wiskott-Aldrich syndrome (WAS) is a severe X-linked primary immunodeficiency resulting from a diversity of mutations distributed across all 12 exons of the WAS gene. WAS encodes a hematopoietic-specific and developmentally regulated cytoplasmic protein (WASp). The objective of this study was to develop a gene correction strategy potentially applicable to most WAS patients by employing nuclease-mediated, site-specific integration of a corrective WAS gene sequence into the endogenous WAS chromosomal locus. In this study, we demonstrate the ability to target the integration of WAS2-12-containing constructs into intron 1 of the endogenous WAS gene of primary CD34+ hematopoietic stem and progenitor cells (HSPCs), as well as WASp-deficient B cell lines and WASp-deficient primary T cells. This intron 1 targeted integration (TI) approach proved to be quite efficient and restored WASp expression in treated cells. Furthermore, TI restored WASp-dependent function to WAS patient T cells. Edited CD34+ HSPCs exhibited the capacity for multipotent differentiation to various hematopoietic lineages in vitro and in transplanted immunodeficient mice. This methodology offers a potential editing approach for treatment of WAS using patient's CD34+ cells.

12.
Med Eng Phys ; 123: 104081, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38365335

RESUMO

BACKGROUND: Shape memory alloys (SMAs) are well-known for their unique ability to undergo a shape change in response to a thermal stimulus. A frequently-used SMA for biomedical devices is NiTi, although its superelastic features tend to be emphasized more than the ability to change shape. Minimally invasive NiTi implants which can reconfigure or adjust their shape across several temperature points could provide desirable surgical outcomes. For decades, therapeutic ultrasound has been used medically as a non-invasive method for tissue thermal therapy. Ultrasound's ability to quickly raise temperatures, and transcutaneously activate shape changes in NiTi implants is a novel approach for eliciting the martensitic thermoelastic transformation. METHODS: The purpose of this study was to investigate the features of therapeutic ultrasound that correspond with temperature changes in different NiTi specimens. For this purpose, ultrasound was applied to two NiTi specimens for two minutes each at varying low- and high-frequency and power settings using a Sonicator 740 and a Dynatron 150. FINDINGS: The baseline temperature for all 32 trials was room temperature (23.0 ± 1.7°C). This study successfully increased the specimen temperature with the application of Sonicator 740 and Dynatron 150 therapeutic ultrasound machines (2.2 ± 2.4°C and 1.5 ± 1.15°C, respectively). From the statistical analyses of the experimental data, it was clear that there is a significant difference between low- and high-power settings on mean temperature change using the Dynatron 150 (ANCOVA; p = 0.013). Interpretation Of clinical relevance, NiTi implants can quickly and easily increase in temperature when applying therapeutic ultrasound. Ultrasound power causes temperature changes and should be accounted for when designing orthopedic implants for applications where dimensional changes are desirable.


Assuntos
Próteses e Implantes , Titânio , Temperatura
13.
Med Phys ; 51(4): 2882-2892, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38308822

RESUMO

BACKGROUND: Minimally invasive procedures usually require navigating a microcatheter and guidewire through endoluminal structures such as blood vessels and airways to sites of the disease. For numerous clinical applications, two-dimensional (2D) fluoroscopy is the primary modality used for real-time image guidance during navigation. However, 2D imaging can pose challenges for navigation in complex structures. Real-time 3D visualization of devices within the anatomic context could provide considerable benefits for these procedures. Continuous-sweep limited angle (CLA) fluoroscopy has recently been proposed to provide a compromise between conventional rotational 3D acquisitions and real-time fluoroscopy. PURPOSE: The purpose of this work was to develop and evaluate a noniterative 3D device reconstruction approach for CLA fluoroscopy acquisitions, which takes into account endoluminal topology to avoid impossible paths between disconnected branches. METHODS: The algorithm relies on a static 3D roadmap (RM) of vessels or airways, which may be generated from conventional cone beam CT (CBCT) acquisitions prior to navigation. The RM is converted to a graph representation describing its topology. During catheter navigation, the device is segmented from the live 2D projection images using a deep learning approach from which the centerlines are extracted. Rays from the focal spot to detector pixels representing 2D device points are identified and intersections with the RM are computed. Based on the RM graph, a subset of line segments is selected as candidates to exclude device paths through disconnected branches of the RM. Depth localization for each point along the device is then performed by finding the point closest to the previous 3D reconstruction along the candidate segments. This process is repeated as the projection angle changes for each CLA image frame. The approach was evaluated in a phantom study in which a catheter and guidewire were navigated along five pathways within a complex vessel phantom. The result was compared to static cCBCT acquisitions of the device in the final position. RESULTS: The average root mean squared 3D distance between CLA reconstruction and reference centerline was 1.87 ± 0.30 $1.87 \pm 0.30$ mm. The Euclidean distance at the device tip was 2.92 ± 2.35 $2.92 \pm 2.35$ mm. The correct pathway was identified during reconstruction in 100 % $100\%$ of frames ( n = 1475 $n=1475$ ). The percentage of 3D device points reconstructed inside the 3D roadmap was 91.83 ± 2.52 % $91.83 \pm 2.52\%$ with an average distance of 0.62 ± 0.30 $0.62 \pm 0.30$ mm between the device points outside the roadmap and the nearest point within the roadmap. CONCLUSIONS: This study demonstrates the feasibility of reconstructing curvilinear devices such as catheters and guidewires during endoluminal procedures including intravascular and transbronchial interventions using a noniterative reconstruction approach for CLA fluoroscopy. This approach could improve device navigation in cases where the structure of vessels or airways is complex and includes overlapping branches.


Assuntos
Catéteres , Imageamento Tridimensional , Imageamento Tridimensional/métodos , Imagens de Fantasmas , Tomografia Computadorizada de Feixe Cônico , Fluoroscopia/métodos
14.
Plant J ; 118(5): 1689-1698, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38310596

RESUMO

Confocal microscopy has greatly aided our understanding of the major cellular processes and trafficking pathways responsible for plant growth and development. However, a drawback of these studies is that they often rely on the manual analysis of a vast number of images, which is time-consuming, error-prone, and subject to bias. To overcome these limitations, we developed Dot Scanner, a Python program for analyzing the densities, lifetimes, and displacements of fluorescently tagged particles in an unbiased, automated, and efficient manner. Dot Scanner was validated by performing side-by-side analysis in Fiji-ImageJ of particles involved in cellulose biosynthesis. We found that the particle densities and lifetimes were comparable in both Dot Scanner and Fiji-ImageJ, verifying the accuracy of Dot Scanner. Dot Scanner largely outperforms Fiji-ImageJ, since it suffers far less selection bias when calculating particle lifetimes and is much more efficient at distinguishing between weak signals and background signal caused by bleaching. Not only does Dot Scanner obtain much more robust results, but it is a highly efficient program, since it automates much of the analyses, shortening workflow durations from weeks to minutes. This free and accessible program will be a highly advantageous tool for analyzing live-cell imaging in plants.


Assuntos
Processamento de Imagem Assistida por Computador , Microscopia Confocal , Software , Processamento de Imagem Assistida por Computador/métodos , Microscopia Confocal/métodos , Células Vegetais
15.
Hepatol Commun ; 8(2)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38315140

RESUMO

BACKGROUND: Minimal hepatic encephalopathy (MHE) negatively affects the prognosis of cirrhosis, but treatment is not standard. Rifamycin SV MMX (RiVM) is a nonabsorbable rifampin derivative with colonic action. METHODS: In a phase 2 placebo-controlled, double-blind randomized clinical trial patients with MHE were randomized to RiVM or placebo for 30 days with a 7-day follow-up. The primary endpoint was a change in stool cirrhosis dysbiosis ratio. Gut-brain (cognition, stool/salivary microbiome, ammonia, brain magnetic resonance spectroscopy), inflammation (stool calprotectin/serum cytokines), patient-reported outcomes (sickness impact profile: total/physical/psychosocial, high = worse), and sarcopenia (handgrip, bioelectric impedance) were secondary. Between/within groups and delta (post-pre) comparisons were performed. RESULTS: Thirty patients (15/group) were randomized and completed the study without safety concerns. While cirrhosis dysbiosis ratio was statistically similar on repeated measures ANOVA (95% CI: -0.70 to 3.5), ammonia significantly reduced (95% CI: 4.4-29.6) in RiVM with changes in stool microbial α/ß-diversity. MHE status was unchanged but only serial dotting (which tests motor strength) improved in RiVM-assigned patients. Delta physical sickness impact profile (95% CI: 0.33 = 8.5), lean mass (95% CI: -3.3 to -0.9), and handgrip strength (95% CI: -8.1 to -1.0) improved in RiVM versus placebo. Stool short-chain fatty acids (propionate, acetate, and butyrate) increased post-RiVM. Serum, urine, and stool bile acid profile changed to nontoxic bile acids (higher hyocholate/ursodeoxycholate and lower deoxycholate/lithocholate) post-RiVM. Serum IL-1ß and stool calprotectin decreased while brain magnetic resonance spectroscopy showed higher glutathione concentrations in RiVM. CONCLUSIONS: RiVM is well tolerated in patients with MHE with changes in stool microbial composition and function, ammonia, inflammation, brain oxidative stress, and sarcopenia-related parameters without improvement in cognition. RiVM modulates the gut-brain axis and gut-muscle axis in cirrhosis.


Assuntos
Encefalopatia Hepática , Rifamicinas , Sarcopenia , Humanos , Amônia , Disbiose/complicações , Força da Mão , Sarcopenia/complicações , Encefalopatia Hepática/tratamento farmacológico , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Inflamação , Músculos , Complexo Antígeno L1 Leucocitário/uso terapêutico
16.
Prostate ; 84(3): 237-244, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37899635

RESUMO

BACKGROUND: Prostate cancer (PCa) parenchymal brain metastases are uncommon and troubling observations in the course of the disease. Our study aims to evaluate the prevalence of brain metastases among PCa patients while reporting various therapeutic modalities, clinical features, and oncological outcomes. METHODS: We retrospectively identified 34 patients with parenchymal brain metastasis out of 4575 patients using a prospectively maintained database that contains clinicopathologic characteristics of PCa patients between January 2012 and December 2021. Based on the three treatment modalities used, the patients were divided into three groups: stereotactic radiosurgery (SRS), whole brain radiotherapy (WBRT), and systemic therapy alone. The Kaplan-Meier curve was used to calculate overall survival [OS] probability and the Cox proportional hazards regression model was used to compare between groups. RESULTS: At the time of brain metastasis diagnosis, the median age was 66 years, the median (interquartile range [IQR]) prostate-specific antigen (PSA) was 2.2 (0.1-26.6) ng/ml and the median (IQR) months from initial PCa diagnosis to brain metastasis development was 70.8 (27.6-100.9). The median (IQR) primary Gleason score was 8 (7-9) and over a median (IQR) follow-up time of 2.2 (1.2-16.5) months, 76.5% (n = 26) of the patients died. Thirteen (38.2%) patients had solitary lesion, whereas 21 (61.8%) had ≥2 lesions. The lesions were supratentorial in 19 (55.9%) patients, infratentorial in six (17.6%), and both sides in nine (26.5%). Among all 34 patients, 10 (29.4%) were treated with SRS, seven (20.6%) with WBRT, and 17 (50%) with systemic therapy alone. OS varied greatly between the three treatment modalities (log-rank test, p = 0.049). Those who were treated with SRS and WBRT had better OS compared with patients who were treated with systemic therapy alone (hazard ratio: 0.37, 95% confidence interval: 0.16-0.86, p = 0.022). CONCLUSIONS: In our single-institutional study, we confirmed that PCa brain metastasis is associated with poor survival outcomes and more advanced metastatic disease. Furthermore, we found that SRS and WBRT for brain metastasis in patients with recurrent PCa appear to be associated with improved OS as compared with systemic therapy alone and are likely secondary to selection bias.


Assuntos
Neoplasias Encefálicas , Neoplasias da Próstata , Radiocirurgia , Masculino , Humanos , Lactente , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/secundário , Neoplasias da Próstata/cirurgia
17.
Surg Endosc ; 38(2): 931-941, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37910247

RESUMO

BACKGROUND: Laparoscopic cholecystectomy with common bile duct exploration (LCBDE) is equivalent in safety and efficacy to endoscopic retrograde cholangiopancreatography (ERCP) plus laparoscopic cholecystectomy (LC) while decreasing number of procedures and length of stay (LOS). Despite these advantages LCBDE is infrequently utilized. We hypothesized that formal, simulation-based training in LCBDE would result in increased utilization and improve patient outcomes across participating institutions. METHODS: Data was obtained from an on-going multi-center study in which simulator-based transcystic LCBDE training curricula were instituted for attending surgeons and residents. A 2-year retrospective review of LCBDE utilization prior to LCBDE training was compared to utilization up to 2 years after initiation of training. Patient outcomes were analyzed between LCBDE strategy and ERCP strategy groups using χ2, t tests, and Wilcoxon rank tests. RESULTS: A total of 50 attendings and 70 residents trained in LCBDE since November 2020. Initial LCBDE utilization rate ranged from 0.74 to 4.5%, and increased among all institutions after training, ranging from 9.3 to 41.4% of cases. There were 393 choledocholithiasis patients analyzed using LCBDE (N = 129) and ERCP (N = 264) strategies. The LCBDE group had shorter median LOS (3 days vs. 4 days, p < 0.0001). No significant differences in readmission rates between LCBDE and ERCP groups (4.7% vs. 7.2%, p = 0.33), or in post-procedure pancreatitis (0.8% v 0.8%, p > 0.98). In comparison to LCBDE, the ERCP group had higher rates of bile duct injury (0% v 3.8%, p = 0.034) and fluid collections requiring intervention (0.8% v 6.8%, p < 0.009) secondary to cholecystectomy complications. Laparoscopic antegrade balloon sphincteroplasty had the highest technical success rate (87%), followed by choledochoscopic techniques (64%). CONCLUSION: Simulator-based training in LCBDE results in higher utilization rates, shorter LOS, and comparable safety to ERCP plus cholecystectomy. Therefore, implementation of LCBDE training is strongly recommended to optimize healthcare utilization and management of patients with choledocholithiasis.


Assuntos
Colecistectomia Laparoscópica , Coledocolitíase , Laparoscopia , Humanos , Coledocolitíase/cirurgia , Ducto Colédoco/cirurgia , Colangiopancreatografia Retrógrada Endoscópica/métodos , Colecistectomia Laparoscópica/métodos , Estudos Retrospectivos , Tempo de Internação
18.
Am J Phys Med Rehabil ; 103(4): e36-e39, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37903617

RESUMO

ABSTRACT: There are many types of cysts in the leg; the most common is a popliteal (Baker's) cyst. This occurs when synovial fluid fills the tissue plane between the medial head of the gastrocnemius and the semimembranosus muscle and is often associated with intraarticular knee pathology. Treatment for various types of cysts includes aspiration with or without fenestration, injections with corticosteroids, dextrose, or various sclerosing agents, and surgical excision. This case describes a 58-yr-old man with a large cyst measuring 14.7 × 2.7 × 3.1 cm in size in the lateral calf, within the lateral gastrocnemius, with atypical size and location for a calf cyst. Computed tomography arthrogram showed intraarticular communication with the knee. The cyst recurred after two aspirations and injections with 25% dextrose/lidocaine. Aspiration and injection with doxycycline resulted in temporary relief followed by recurrence. Complete cyst resolution occurred after final aspiration without injectate. The cyst was likely synovial based on location, intraarticular communication, and fluid analysis. We suspect that complete resolution may have been due to repeated aspiration and injection, essentially performing longitudinal cyst fenestration, with possible contribution from doxycycline injection. Further study of intracyst doxycycline injection with reaspiration after 10 mins for treatment of refractory cysts may be warranted.


Assuntos
Cistos , Cisto Popliteal , Masculino , Humanos , Cisto Popliteal/diagnóstico por imagem , Cisto Popliteal/terapia , Escleroterapia/métodos , Doxiciclina/uso terapêutico , Perna (Membro)/patologia , Cistos/diagnóstico por imagem , Cistos/tratamento farmacológico , Glucose
19.
Am J Gastroenterol ; 119(5): 977-981, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38153339

RESUMO

Lactulose-based hepatic encephalopathy treatment requires bowel movements/day titration, which is improved with Bristol stool scale (BSS) incorporation. Dieta app evaluates artificial intelligence (AI)-based BSS (AI-BSS) with stool images. Initially, controls (N = 13) and cirrhosis patients on lactulose/not on lactulose (n = 33) were trained on the app. They entered self-reported BSS (self-BSS) with AI-BSS communicated. Lactulose dose changes were tracked. A subset (n = 12) was retested with AI communication blocked. Most subjects were comfortable with the app. Self/AI-BSS and lactulose dose/AI-BSS correlation increased with app use. AI-BSS communications improved insight into self-BSS over time. Dieta app to gauge stool AI characteristics was acceptable and increased insight into lactulose dose and BSS in cirrhosis.


Assuntos
Inteligência Artificial , Fezes , Fármacos Gastrointestinais , Encefalopatia Hepática , Lactulose , Aplicativos Móveis , Smartphone , Humanos , Encefalopatia Hepática/terapia , Lactulose/uso terapêutico , Lactulose/administração & dosagem , Masculino , Feminino , Fezes/química , Pessoa de Meia-Idade , Fármacos Gastrointestinais/uso terapêutico , Fármacos Gastrointestinais/administração & dosagem , Idoso , Cirrose Hepática/complicações , Adulto
20.
Prostate ; 84(4): 395-402, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38108113

RESUMO

BACKGROUND: We sought to characterize and compare late patient-reported outcomes (PROs) after moderately hypofractionated intensity modulated radiation therapy (IMRT) and proton beam therapy (PBT) for localized prostate cancer (PC). METHODS: This multi-institutional analysis included low- or intermediate-risk group PC patients treated with moderately hypofractionated radiation to an intact prostate stratified by treatment modality: IMRT or PBT. The primary outcomes were prospectively collected patient-reported late gastrointestinal (GI) and genitourinary (GU) toxicity assessed by International Prostate Symptom Score (IPSS) and Expanded PC Index Composite (EPIC). Multivariable regression analysis (MVA) controlling for age, race, and risk group tested the effect of time, treatment, and their interaction. RESULTS: 287 IMRT and 485 PBT patients were included. Intermediate risk group (81.2 vs. 68.2%; p < 0.001) and median age at diagnosis (70 vs. 67 years; p < 0.001) were higher in the IMRT group. On MVA, there was no significant difference between modalities. PBT IPSS did not differ from IMRT IPSS at 12 months (odds ratio [OR], 1.19; p = 0.08) or 24 months (OR, 0.99; p = 0.94). PBT EPIC overall GI function at 12 months (OR, 3.68; p = 0.085) and 24 months (OR 2.78; p = 0.26) did not differ from IMRT EPIC overall GI function. At 24 months, urinary frequency was no different between PBT and IMRT groups (OR 0.35; p = 0.096). CONCLUSIONS: This multi-institutional analysis of low- or intermediate-risk PC treated with moderately hypofractionated PBT and IMRT demonstrated low rates of late patient-reported GI and GU toxicities. After covariate adjustment, late GI and GU PROs were not significantly different between PBT or IMRT cohorts.


Assuntos
Neoplasias da Próstata , Terapia com Prótons , Radioterapia de Intensidade Modulada , Masculino , Humanos , Radioterapia de Intensidade Modulada/efeitos adversos , Terapia com Prótons/efeitos adversos , Neoplasias da Próstata/radioterapia , Próstata/efeitos da radiação , Medidas de Resultados Relatados pelo Paciente
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