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1.
Ophthalmic Plast Reconstr Surg ; 40(2): 181-186, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37995134

RESUMO

PURPOSE: To identify the effects of Rho Kinase (ROCK) inhibitor medications on human orbital adipogenesis, fibroblast proliferation, and fibrosis. METHODS: Orbital adipose tissue was obtained from patients with Graves' ophthalmopathy (GO) as well as controls (non-GO or normal) after informed consent was done. These tissue samples were cultured and adipogenesis was initiated. Levels of Rho Kinase as well as cellular mediators of orbital inflammation and fibrosis. The same cultures and measurements were then repeated with the use of a ROCK inhibitor (KD025-ROCK2) to assess for changes in adipogenesis as well as markers associated with inflammation and fibrosis. RESULTS: Rho Kinase levels in GO tissue were more highly expressed than in controls. These levels were suppressed with the use of the ROCK inhibitor KD025. There was a dose-dependent reduction in differentiation of orbital adipocytes with the use of KD025. KD025 reduced the levels of fibrosis-related gene expression. Finally, there was a significant reduction of transforming growth factor beta mediated phosphorylation signaling pathways in the KD025-treated GO tissue. CONCLUSION: This study shows that the ROCK inhibitor, KD025, helps to reduce the expression of ROCK in GO tissue along with reducing orbital adipocyte differentiation as well as cell mediators involved in fibrosis that occurs in GO.


Assuntos
Oftalmopatia de Graves , Quinases Associadas a rho , Humanos , Oftalmopatia de Graves/tratamento farmacológico , Adipócitos , Inflamação , Inibidores de Proteínas Quinases/farmacologia , Fibrose
2.
Ophthalmic Plast Reconstr Surg ; 38(5): 496-502, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35502804

RESUMO

PURPOSE: To review the demographics, clinical features, and response of orbital squamous cell carcinoma treated with cemiplimab. METHODS: This is a retrospective multi-institutional series. Patient characteristics, drug dosing, duration, and response to treatment were evaluated. RESULTS: The study cohort consisted of 11 patients from 5 institutions. All patients received a regimen of 350 mg q 3 weeks and an average of 11.2 cycles (SD 5.8). No patient experienced significant side effects requiring treatment or cessation of cemiplimab. Complete response was achieved in 9 patients (82%) treated with cemiplimab. CONCLUSIONS: Immune checkpoint inhibitors, such as cemiplimab provide a globe-sparing option for the treatment of orbital squamous cell carcinoma. It is important to consider these agents especially when orbital exenteration is the alternative.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Orbitárias , Neoplasias Cutâneas , Anticorpos Monoclonais Humanizados/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Humanos , Neoplasias Orbitárias/tratamento farmacológico , Estudos Retrospectivos , Neoplasias Cutâneas/tratamento farmacológico
3.
Curr Cardiol Rep ; 23(11): 164, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34599422

RESUMO

PURPOSE OF REVIEW: Our understanding of the fundamental cellular and molecular factors leading to atrial fibrillation (AF) remains stagnant despite significant advancement in ablation and device technologies. Diagnosis and prevention strategies fall behind that of treatment, but expanding knowledge in AF genetics holds the potential to drive progress. We aim to review how an understanding of the genetic contributions to AF can guide an approach to individualized risk stratification and novel avenues in drug discovery. RECENT FINDINGS: Rare familial forms of AF identified monogenic contributions to the development of AF. Genome-wide association studies (GWAS) further identified single-nucleotide polymorphisms (SNPs) suggesting polygenic and multiplex nature of this common disease. Polygenic risk scores accounting for the multitude of associated SNPs that each confer mildly elevated risk have been developed to translate genetic information into clinical practice, though shortcomings remain. Additionally, novel laboratory methods have been empowered by recent genetic findings to enhance drug discovery efforts. AF is increasingly recognized as a disease with a significant genetic component. With expanding sequencing technologies and accessibility, polygenic risk scores can help identify high risk individuals. Advancement in digital health tools, artificial intelligence and machine learning based on standard electrocardiograms, and genomic driven drug discovery may be integrated to deliver a sophisticated level of precision medicine in this modern era of emphasis on prevention. Randomized, prospective studies to demonstrate clinical benefits of these available tools are needed to validate this approach.


Assuntos
Fibrilação Atrial , Inteligência Artificial , Fibrilação Atrial/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genômica , Humanos , Estudos Prospectivos
4.
Pacing Clin Electrophysiol ; 41(7): 870-871, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29746708

RESUMO

A 72-year-old man who underwent a left atrial appendage (LAA) closure device 2 years ago presented with atrial flutter with rapid ventricular rate and was referred for cardioversion. Precardioversion transesophageal echocardiogram showed left atrial thrombus and therefore the procedure was aborted. Currently, there is no guideline on imaging surveillance or anticoagulation in patients with LAA closure device who develop intracardiac thrombus after the initial 6-month surveillance period.


Assuntos
Apêndice Atrial/cirurgia , Cardiopatias/etiologia , Complicações Pós-Operatórias/etiologia , Próteses e Implantes/efeitos adversos , Trombose/etiologia , Idoso , Átrios do Coração , Humanos , Masculino , Fatores de Tempo
5.
Respiration ; 96(6): 543-551, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30114688

RESUMO

BACKGROUND: Associated pulmonary hypertension (APH) is frequently observed in fibrosing interstitial pneumonias (FIP), such as idiopathic pulmonary fibrosis (IPF). APH is associated with worse prognosis, but it remains unclear whether it is associated with greater functional impairment. Six-minute walk distance (6MWD) is widely used to assess functional capacity in pulmonary hypertension and FIP. OBJECTIVES: To investigate if APH independently contributes to exercise intolerance in FIP, irrespective of the extent of underlying fibrosis. METHODS: Patients diagnosed with FIP (September 2009 to June 2017) were included in the study if they underwent right heart catheterization, high-resolution chest computed tomography (HRCT), and 6MWD within 3 months. Recruitment was not limited only to patients undergoing lung transplant assessment. APH was defined as mean pulmonary artery pressure (mPAP) ≥25 mm Hg. The extent of fibrosis was quantified on HRCT using a visual fibrosis score by 2 separate observers. RESULTS: Seventy-two patients (60 with IPF) were identified. Fifty-five patients had APH. mPAP was not significantly different in subgroups stratified according to the extent of fibrosis on HRCT. Pulmonary vascular resistance (PVR) was the strongest predictor of 6MWD on both univariate and stepwise regression analyses, and remained so considering only patients with normal wedge pressure (< 15 mm Hg) (n = 61). HRCT fibrosis score and pulmonary function tests did not significantly correlate with 6MWD. CONCLUSIONS: In patients with FIP, PVR is a significant contributor of 6MWD, independently from the extent of fibrosis on HRCT. These results strengthen both the rationale to use 6MWD as endpoint in FIP and to target APH with specific therapies.


Assuntos
Tolerância ao Exercício , Hipertensão Pulmonar/fisiopatologia , Fibrose Pulmonar Idiopática/fisiopatologia , Idoso , Estudos Transversais , Teste de Esforço , Humanos , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/diagnóstico por imagem , Fibrose Pulmonar Idiopática/complicações , Pessoa de Meia-Idade , Estudos Retrospectivos
6.
Crit Care Med ; 45(8): 1285-1294, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28489648

RESUMO

OBJECTIVE: Angiotensin II is an endogenous hormone with vasopressor and endocrine activities. This is a systematic review of the safety of IV angiotensin II. DATA SOURCES: PubMed, Medline, Scopus, and Cochrane. STUDY SELECTION: Studies in which human subjects received IV angiotensin II were selected whether or not safety was discussed. DATA EXTRACTION: In total, 18,468 studies were screened by two reviewers and one arbiter. One thousand one hundred twenty-four studies, in which 31,281 participants received angiotensin II (0.5-3,780 ng/kg/min), were selected. Data recorded included number of subjects, comorbidities, angiotensin II dose and duration, pressor effects, other physiologic and side effects, and adverse events. DATA SYNTHESIS: The most common nonpressor effects included changes in plasma aldosterone, renal function, cardiac variables, and electrolytes. Adverse events were infrequent and included headache, chest pressure, and orthostatic symptoms. The most serious side effects were exacerbation of left ventricular failure in patients with congestive heart failure and bronchoconstriction. One patient with congestive heart failure died from refractory left ventricular failure. Refractory hypotensive shock was fatal in 55 of 115 patients treated with angiotensin II in case studies, cohort studies, and one placebo-controlled study. One healthy subject died after a pressor dose of angiotensin II was infused continuously for 6 days. No other serious adverse events attributable to angiotensin II were reported. Heterogeneity in study design prevented meta-analysis. CONCLUSION: Adverse events associated with angiotensin II were infrequent; however, exacerbation of asthma and congestive heart failure and one fatal cerebral hemorrhage were reported. This systematic review supports the notion that angiotensin II has an acceptable safety profile for use in humans.


Assuntos
Angiotensina II/efeitos adversos , Angiotensina II/farmacologia , Angiotensina II/administração & dosagem , Humanos , Injeções Intravenosas
7.
Ophthalmic Plast Reconstr Surg ; 33(3S Suppl 1): S114-S116, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28099230

RESUMO

A 56-year-old male with history of chronic sinusitis was found to have a 3 cm left orbital lesion on CT. Subsequent MRI demonstrated a multilobulated enhancing soft tissue lesion at the superotemporal region of the left orbit. Initial biopsy was reported as a low-grade sarcoma. On further evaluation, a consensus was made that the lesion was likely a benign mixed mesenchymal type tumor but should nonetheless be surgically removed. Left lateral orbitotomy was performed which revealed a tumor originating in the lateral orbital bone with segments eroding through the wall of the orbit. Intraoperative frozen sections revealed myoepitheliod tissue with locally aggressive features and the tumor was completely removed. The final histopathologic analysis of the tissue was consistent with a chondromyxoid fibroma. Chondomyxoid fibroma is a rare entity in the orbital bones and is more commonly seen in long bones.


Assuntos
Condroblastoma/diagnóstico , Fibroma/diagnóstico , Órbita/patologia , Neoplasias Orbitárias/diagnóstico , Biópsia , Diagnóstico Diferencial , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Doenças Raras
8.
World J Urol ; 33(1): 93-7, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24671610

RESUMO

PURPOSE/OBJECTIVE(S): Recent in vitro and in vivo evidence has suggested that statin medications may have anticancer activity. We sought to determine whether statin use was associated with improved clinical outcome in men treated with brachytherapy for prostate cancer. MATERIALS/METHODS: A database of men with prostate cancer treated with permanent Iodine-125 brachytherapy between January 1999 and February 2009 was retrospectively analyzed. Standard guidelines (i.e., American Brachytherapy Society selection criteria) were used for selecting patients for brachytherapy. Biochemical failure was defined using the Phoenix definition. RESULTS: From a total of 247 men with prostate adenocarcinoma treated with brachytherapy, 174 patients (70 %) were identified as using statin medications, either during initial visit or during follow-up. Median PSA follow-up was 51 months after date of implant (range 9.4-140.35). Overall biochemical failure rate was 7.3 % (18 patients). On univariate analysis, statin use was associated with significantly improved freedom from biochemical failure [hazard ratio (HR) 0.28; 95 % CI 0.10-0.72; p < 0.01 by log-rank test]. In multivariate Cox analysis performed with the variables statin use, pretreatment PSA, clinical T stage, Gleason score, and D90 or V100, statin use remained significantly associated with improved freedom from biochemical failure (HR 0.288; 95 % CI 0.086-0.886; p = 0.0299). CONCLUSIONS: Statin use was associated with a significant improvement in freedom from biochemical failure in this cohort of men treated with brachytherapy for prostate cancer. Further investigation into the favorable effect of statin use on brachytherapy and radiation therapy in general is warranted, including prospective trials.


Assuntos
Adenocarcinoma/radioterapia , Braquiterapia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Recidiva Local de Neoplasia/epidemiologia , Neoplasias da Próstata/radioterapia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
9.
Clin Orthop Relat Res ; 473(8): 2680-7, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25917424

RESUMO

BACKGROUND: Heterotopic ossification (HO) develops after nearly 2/3 of traumatic blast amputations in the contemporary battlefield. This phenomenon has potentially devastating consequences for servicemen and women and its pathophysiology warrants further investigation using a previously developed animal blast model. QUESTIONS/PURPOSES: We asked, what is the (1) severity (quantity) and (2) type (location) of HO bone formation after a hindlimb blast amputation with two distinct blast media. We hypothesized that a more "war-relevant" blast medium could be a more accurate model and potentially intensify the development of HO. METHODS: Using a Sprague-Dawley rat model, the pathophysiology of ectopic bone formation in a traumatic hindlimb blast amputation was evaluated. Twenty-four animals underwent blast amputations and closure based on a previously established experimental model. Half the amputations were subjected to blasted sand and the other 1/2 to blasted water. Serial orthogonal radiography was performed on each animal until euthanasia at 24 weeks to track the development of HO. Heterotopic bone severity and type were assessed by three independent graders at each time using a novel grading scale to assess quantity and quality of HO. RESULTS: All animals had radiographic evidence of HO develop. No differences were observed in ectopic bone development between sand and water blasting regarding severity or type at any time. Animals that received water and sand blasting had moderate HO develop at 24 weeks (median, 2.0 and 2.5 weeks, respectively; range, 1-3 weeks; difference of medians, 0.5; p=0.67). At the time of euthanasia, 10 animals that were water blasted had Type 3 HO compared with 11 in the sand-blasted group (p=1.00). CONCLUSIONS: Our study showed a clear development of HO after hindlimb blast amputation in a Sprague-Dawley rat model; however, no difference was observed in HO development based on the type of blast media. This suggests it is the blast mechanism that induces ectopic bone development, regardless of the blasted medium. The grading scale we developed for our animal-model study provided a reliable means of assessing HO severity and type. CLINICAL RELEVANCE: We anticipate that future investigations will elucidate similarities between service members' wartime extremity injuries and the animal model used in our study, and with focused future research this model may have beneficial therapeutic implications as the pathophysiology of HO development is further understood.


Assuntos
Amputação Traumática/etiologia , Traumatismos por Explosões/etiologia , Membro Posterior/lesões , Ossificação Heterotópica/etiologia , Amputação Traumática/diagnóstico por imagem , Amputação Traumática/fisiopatologia , Amputação Traumática/cirurgia , Animais , Traumatismos por Explosões/diagnóstico por imagem , Traumatismos por Explosões/fisiopatologia , Traumatismos por Explosões/cirurgia , Modelos Animais de Doenças , Membro Posterior/diagnóstico por imagem , Membro Posterior/fisiopatologia , Masculino , Ossificação Heterotópica/diagnóstico por imagem , Ossificação Heterotópica/fisiopatologia , Radiografia , Ratos Sprague-Dawley , Índice de Gravidade de Doença , Fatores de Tempo
10.
AJR Am J Roentgenol ; 203(5): 1104-8, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25341151

RESUMO

OBJECTIVE: The purpose of this study was to define baseline variability of apparent diffusion coefficient (ADC) on diffusion-weighted MR imaging (DWI) in patients with head and neck squamous cell carcinoma (HNSCC) and to compare it with early treatment-induced ADC change. SUBJECTS AND METHODS: Patients with American Joint Committee on Cancer stages III and IV HNSCC were imaged with two baseline DWI examinations 1 week apart and a third DWI examination during the 2nd week of curative-intent chemoradiation therapy. Mean ADC was measured in the primary tumor and largest lymph node for each patient on the three DWI scans. Mean baseline percentage differences (%∆ADC) were compared with intratreatment change. The repeatability coefficient for baseline %∆ADC was calculated and compared with intratreatment %∆ADC. Repeatability was also assessed with Bland-Altman plots and the intraclass correlation coefficient (ICC). RESULTS: Sixteen patients underwent double baseline imaging, with 14 also undergoing intratreatment imaging. Baseline nodal disease ADC could be measured in 16 patients, but ADC in primary tumors could only be measured in five patients. The nodal mean (SD) baseline %∆ADC was 8% (± 7%), which was significantly different compared with intratreatment changes of 32% (± 31%) (p = 0.01). Baseline ICC was 0.86 for nodal disease and 0.99 for primary tumor (excellent correlation). The calculated repeatability coefficient for baseline nodal ADC was 15%. No patients had decreases in intratreatment ADC of more than 15%. CONCLUSION: Baseline ADC variability for HNSCC is less than intratreatment ADC change for nodal disease. Assessment of response should consider intrinsic baseline variability.


Assuntos
Algoritmos , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia , Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/patologia , Interpretação de Imagem Assistida por Computador/métodos , Adulto , Idoso , Feminino , Humanos , Aumento da Imagem/métodos , Masculino , Pessoa de Meia-Idade , Prognóstico , Radiografia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Carcinoma de Células Escamosas de Cabeça e Pescoço , Resultado do Tratamento
12.
BMC Nephrol ; 15: 39, 2014 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-24571546

RESUMO

BACKGROUND: An analysis of intracranial hemorrhage (ICH) in a national sample of autosomal dominant polycystic kidney disease (ADPKD) patients receiving long-term dialysis has not been reported. It is often assumed that patients with ADPKD are not at increased risk of ICH after starting dialysis. We hypothesized that patients with ADPKD would have a higher subsequent risk of ICH even after the start of chronic dialysis. METHODS: Retrospective cohort study of Medicare primary patients with and without ADPKD in the United States Renal Data System (USRDS), initiated on chronic dialysis or transplanted between 1 January 1999 and 3 July 2009, and followed until 31 December 2009. Covariates included age, gender, race, prior stroke, diabetes mellitus, dialysis modality, body mass index, serum albumin and other co-morbid conditions from the Medical Evidence Form. Primary outcome was ICH, based on inpatient and outpatient Medicare claims, and all-cause mortality. Kaplan-Meier analysis was used for unadjusted assessment of time to events. Cox regression was used for assessment of factors associated with ICH and mortality. We performed competing risk regression using kidney transplant and death as competing risks. Kidney transplant was also modeled as a time-dependent covariate in Cox regression. RESULTS: Competing risk regression demonstrated that ADPKD had a subhazard ratio 2.97 for ICH (95% CI 2.27-3.89). Adjusted Cox analysis showed that ADPKD patients had an AHR for death of 0.59 vs. non-ADPKD patients (95% CI 0.57-0.61). CONCLUSIONS: ADPKD is a significant risk factor for ICH among patients on maintenance dialysis. Our Medicare primary cohort was older than in previous studies of intracranial aneurysm rupture among ADPKD patients. There are also limitations inherent to using the USRDS database.


Assuntos
Hemorragias Intracranianas/mortalidade , Falência Renal Crônica/mortalidade , Rim Policístico Autossômico Dominante/mortalidade , Distribuição por Idade , Idoso , Causalidade , Comorbidade , Feminino , Humanos , Masculino , Prevalência , Medição de Risco , Distribuição por Sexo , Taxa de Sobrevida , Estados Unidos/epidemiologia
13.
Neuroophthalmology ; 38(1): 14-20, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-27928268

RESUMO

Myoepitheliomas are rare tumours that originate from glandular tissues such as the parotid or salivary glands, and less commonly from soft tissues of the head, neck, and other parts of the body. Intraorbital myoepitheliomas generally arise from the lacrimal gland. Intracranial myoepitheliomas are rare. We report a myoepithelioma of the orbital apex that did not originate from the lacrimal gland. It extended to the middle cranial fossa from the orbital apex and involved the dura and adjacent bone. A diagnostic biopsy via a lateral orbitotomy preceded resection. We review the natural course and histopathology of myoepithelial neoplasms, the surgical nuances of approaching an orbital apex tumour with maximal functional preservation, and the optimal management practices of these rare lesions.

14.
JACC Clin Electrophysiol ; 10(2): 270-283, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37999669

RESUMO

BACKGROUND: Strokes after left atrial appendage closure (LAAC) prophylaxis are generally less severe than those after warfarin prophylaxis-thought to be secondary to more hemorrhagic strokes with warfarin. Hemorrhagic strokes are similarly infrequent with direct oral anticoagulant (DOAC) prophylaxis, so the primary subtype after either LAAC or DOAC prophylaxis is ischemic stroke (IS). OBJECTIVES: The purpose of this study was to compare the severity of IS using the modified Rankin Scale in atrial fibrillation patients receiving prophylaxis with DOACs vs LAAC. METHODS: A retrospective analysis was performed of consecutive patients undergoing LAAC at 8 centers who developed an IS (ISLAAC) compared with contemporaneous consecutive patients who developed IS during treatment with DOACs (ISDOAC). The primary outcome was disabling/fatal stroke (modified Rankin Scale 3-5) at discharge and 3 months later. RESULTS: Compared with ISDOAC patients (n = 322), ISLAAC patients (n = 125) were older (age 77.2 ± 13.4 years vs 73.1 ± 11.9 years; P = 0.002), with higher HAS-BLED scores (3.0 vs 2.0; P = 0.004) and more frequent prior bleeding events (54.4% vs 23.6%; P < 0.001), but similar CHA2DS2-VASc scores (5.0 vs 5.0; P = 0.28). Strokes were less frequently disabling/fatal with ISLAAC than ISDOAC at both hospital discharge (38.3% vs 70.3%; P < 0.001) and 3 months later (33.3% vs 56.2%; P < 0.001). Differences in stroke severity persisted after propensity score matching. By multivariate regression analysis, ISLAAC was independently associated with fewer disabling/fatal strokes at discharge (OR: 0.22; 95% CI: 0.13-0.39; P < 0.001) and 3 months (OR: 0.25; 95% CI: 0.12-0.50; P < 0.001), and fewer deaths at 3 months (OR: 0.28; 95% CI: 0.12-0.64; P < 0.001). CONCLUSIONS: Ischemic strokes in patients with atrial fibrillation are less often disabling or fatal with LAAC than DOAC prophylaxis.


Assuntos
Fibrilação Atrial , Acidente Vascular Cerebral Hemorrágico , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Varfarina/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/cirurgia , AVC Isquêmico/induzido quimicamente , AVC Isquêmico/complicações , AVC Isquêmico/tratamento farmacológico , Acidente Vascular Cerebral Hemorrágico/induzido quimicamente , Acidente Vascular Cerebral Hemorrágico/complicações , Acidente Vascular Cerebral Hemorrágico/tratamento farmacológico , Estudos Retrospectivos , Oclusão do Apêndice Atrial Esquerdo , Resultado do Tratamento , Anticoagulantes/efeitos adversos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Hemorragia/induzido quimicamente
15.
Clin Toxicol (Phila) ; 61(9): 644-648, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37917043

RESUMO

INTRODUCTION: Thebaine is an alkaloid in poppy seeds that is neurotoxic to animals. Data on its clinical effects and toxicokinetics in people are minimal. In 2022, poppy seeds high in thebaine entered the Australian food market, and people consuming tea made from these poppy seeds developed poisoning. METHODS: Three patients who drank poppy seed tea and developed neuromuscular toxicity consented for thebaine to be quantitated in serial blood samples. Blood samples were analyzed by liquid chromatography with high-resolution mass spectrometry. RESULTS: Case 1: A man in his 60s presented with drowsiness, vomiting, malaise and myoclonus. He developed metabolic acidosis with hyperlactataemia, acute kidney injury requiring haemodialysis, convulsions, rhabdomyolysis, and was in the hospital for 18 days. The admission thebaine blood concentration was 2.1 mg/L, and the apparent elimination half-life was 14.8 h. Case 2: A man in his 30s presented with myoclonus, rigidity, vomiting, and dizziness. He developed metabolic acidosis with hyperlactataemia, acute kidney injury, and myalgias. The admission thebaine blood concentration was 4.1 mg/L, and the apparent elimination half-life was 11.6 h. Case 3: A man in his 30s presented with myoclonus, rigidity, clonus, diaphoresis, and abdominal pain. The admission thebaine blood concentration was 2.2 mg/L, and the apparent elimination half-life was 8.3 h. DISCUSSION: Neuromuscular toxicity, metabolic acidosis with hyperlactataemia, acute kidney injury, and gastrointestinal symptoms were prominent clinical features in these patients after drinking poppy seed tea. Effects persisted for days, and all survived, despite thebaine concentrations far exceeding those in published forensic reports, although human data are sparse. Compared to rats, the thebaine apparent elimination half-life is much longer in humans who develop symptoms at lower concentrations. CONCLUSIONS: Despite relatively high thebaine blood concentrations and moderate to severe poisoning, outcomes were favourable with early presentations. It is possible that acute kidney injury prolongs the apparent elimination half-life of thebaine.


Assuntos
Acidose , Injúria Renal Aguda , Mioclonia , Papaver , Masculino , Humanos , Animais , Ratos , Tebaína/análise , Morfina , Papaver/química , Toxicocinética , Austrália , Sementes/química , Chá , Injúria Renal Aguda/induzido quimicamente , Vômito/induzido quimicamente
16.
Med Phys ; 39(5): 2754-60, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22559646

RESUMO

PURPOSE: To determine whether there is a CT dataset may be more favorable for planning and dose calculation by comparing dosimetric characteristics between treatment plans calculated using free breathing (FB), maximum and average intensity projection (MIP and AIP, respectively) CTs for lung cancer patients receiving stereotactic body radiation therapy (SBRT). METHODS: Twenty lung cancer SBRT patients, treated on a linac with 2.5 mm width multileaf-collimator (MLC), were analyzed retrospectively. Both FB helical and four-dimensional CT scans were acquired for each patient. Internal target volume (ITV) was delineated based on MIP CTs and modified based on both ten-phase datasets and FB CTs. Planning target volume (PTV) was then determined by adding additional setup margin to ITV. The PTVs and beams in the optimized treatment plan based on FB CTs were copied to MIP and AIP CTs, with the same isocenters, MLC patterns and monitor units. Mean effective depth (MED) of beams, and some dosimetric parameters for both PTVs and most important organ at risk (OAR), lung minus PTV, were compared between any two datasets using two-tail paired t test. RESULTS: The MEDs in FB and AIP plans were similar but significantly smaller (Ps < 0.001) than that in MIP plans. Minimum dose, mean dose, dose covering at least 90% and 95% of PTVs in MIP plans were slightly higher than two other plans (Ps < 0.008). The absolute volume of lung minus PTV receiving greater than 5, 10, and 20 Gy in MIP plans were significantly smaller than those in both FB and AIP plans (Ps < 0.008). Conformity index for FB plans showed a small but statistically significantly higher. CONCLUSIONS: Dosimetric characteristics of AIP plans are similar to those of FB plans. Slightly better target volume coverage and significantly lower low-dose region (≤30 Gy) in lung was observed in MIP plans. The decrease in low-dose region in lung was mainly caused by the change of lung volume contoured on two datasets rather than the differences of dose distribution between AIP and MIP plans. Compare with AIP datasets, FB datasets were more prone to significant image artifacts and MIP datasets may overestimate or underestimate the target volume when the target is closer to the denser tissue, so AIP seems favorable for planning and dose calculation for lung SBRT.


Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Radiocirurgia/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Respiração , Tomografia Computadorizada por Raios X/métodos , Humanos , Neoplasias Pulmonares/fisiopatologia , Radiometria
17.
JACC Case Rep ; 4(24): 101614, 2022 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-36684031

RESUMO

Serious adverse events such as hemothorax are rarely seen in catheter ablation for atrial fibrillation. A recent case report discussed hemothorax from injury of the intercostal artery during atrial fibrillation ablation. Our case presents a patient with spontaneous bleeding from the intercostal artery that led to hemothorax, disseminated intravascular coagulation, and death. (Level of Difficulty: Intermediate.).

18.
J Radiosurg SBRT ; 8(1): 47-54, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35387403

RESUMO

Two automated treatment planning techniques were evaluated for multiple brain metastases using a single isocenter. One technique is knowledge-based planning (KBP) using a stereotactic radiosurgery (SRS) model in Eclipse treatment planning system (TPS); and the other is the Multiple Brain Mets (MBM) SRS technique in Brainlab Elements TPS. Eighteen plans each with 3-10 lesions were used for the study. Plan evaluation metrics included the planning target volume (PTV) coverage, conformity index (CI), total monitor units (MUs), plan optimization time, brain V12 Gy, V8 Gy, and V5 Gy. Both the KBP and MBM planning techniques produced comparable plans to the manually generated clinical plans in terms of PTV coverage and CI. For irregularly shaped lesions, the KBP plans provided more conformal dose distribution to the PTV than the MBM plans. The KBP plans took significantly longer time to plan but have fewer MUs than the MBM plans. The MBM plans spared normal brain tissues better than the KBP plans in terms of V5 Gy.

19.
Am J Ophthalmol Case Rep ; 28: 101714, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36217437

RESUMO

Purpose: Localized amyloidosis can affect numerous tissues throughout the body and can also affect a variety of peri-ocular tissues including the conjunctiva, extra-ocular muscles, peri-orbital soft tissue, and lacrimal gland. We report two cases of amyloidosis presenting with eyelid involvement. Observations: The first case represented a more subtle presentation of skin thickening with a pre-septal cellulitis, while the second case had a dramatic presentation of edema evolving into tissue dehiscence and spontaneous hemorrhage with ongoing angioedema and systemic coagulopathy. Conclusions and importance: The two cases of biopsy-proven orbital/peri-ocular amyloidosis demonstrate the different clinical presentations that may go from the subtle to dramatic, depending on which peri-ocular tissues are affected and to what degree. Standards for treatment of amyloidosis remain conservative initially with surgery or radiation recommended only for refractory cases, but additional therapies are under investigation. Clinicians should have high clinical suspicion for amyloidosis with findings such as skin thickening or significant periorbital edema and should always consider tissue biopsy and further workup for amyloidosis if the findings worsen or do not resolve with treatment of more common conditions such as cellulitis.

20.
Data Brief ; 42: 108080, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35434219

RESUMO

Optical microscopy images and confocal data for Aerosol Jet Printed (AJP) lines over a 16 hour print duration is provide in this dataset ("Mapping Drift in Morphology and Electrical Performance in Aerosol Jet Printing" [1]). Lines were uninterruptedly printed by AJP on a glass substrate using silver nanoparticle ink over a 16-hour time frame. The ink used for this experiment was a 0.6:0.3:0.2 mL mixture of Clariant Prelect TPS 50 G2 silver nanoparticle ink, ethylene glycol, and deionized water, respectively. Deposition was achieved with an Optomec AJ 300-UP Aerosol JetTM Deposition System using a Sprint Series Ultrasonic Atomizer MAX, aerodynamic filtering, and a nozzle having an orifice diameter of 150 µm. The typical focus ratio of 1.75 within standard range was used. The optical microscopic images of 350 µm AJP printed lines at 80 different time points were then selectively collected. Keyence VK-X200 with 150x magnification was used, which provided 50 µm to 267 pixel resolution image with more than 1000 cross-sections at each time point. Filtering of the pixels with outlying heights was performed with a multi-file analyzer. The dataset was primarily collected to understand system-level, temporal drifts in print morphology, which would further allow to predict electrical performance in time domain. Additional purposes for the dataset include: 1) benchmark dataset for morphology and print performance between AJP systems and print settings, 2) test data for new image filtering, segmentation, and classification algorithms and 3) baseline training data for real-time, in situ classification of operational time windows for AJP feedback control.

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