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Tenalisib, a selective phosphoinositide-3-kinase δ/γ, and salt-inducible-kinase-3 inhibitor has shown efficacy and was well-tolerated in patients with T-cell lymphoma (TCL). In vitro studies suggest a synergistic anti-tumor potential for the combination of tenalisib with the histone-deacetylase inhibitor, romidepsin. This multicenter, open-label, phase I/II study was designed to characterize the safety, efficacy and pharmacokinetics of oral tenalisib twice-daily and intravenous romidepsin administered on days 1, 8 and 15 in 28-day cycles in adults with relapsed/refractory TCL. Phase I/dose escalation determined the maximum tolerated dose (MTD)/optimal doses of tenalisib and romidepsin. The phase II/dose expansion assessed the safety and anti-tumor activity of the combination at MTD/optimal dose. Overall, 33 patients were enrolled. In dose escalation, no dose-limiting toxicity was identified. Hence, the recommended doses for dose expansion were tenalisib 800 mg twice daily orally, and romidepsin 14 mg/m2 intravenous. Overall treatment-emergent adverse events of any grade reported in >15% of patients were nausea, thrombocytopenia, increased aspartate aminotransferase, increased alanine aminotransferase, decreased appetite, neutropenia, vomiting, fatigue, anemia, dysgeusia, weight loss, diarrhea, and hypokalemia. Twenty-three patients (69.7%) had related grade ≥3 treatment-emergent adverse events. The overall objective response rate in evaluable patients was 63.0% (peripheral TCL: 75% and cutaneous TCL: 53.3%), with a complete response and partial response of 25.9% and 37.0% respectively. The median duration of response was 5.03 months. Co-administration of tenalisib and romidepsin did not significantly alter the pharmacokinetics of romidepsin. Overall, tenalisib and romidepsin combination demonstrated a favorable safety and efficacy profile supporting its further development for relapsed/refractory TCL (clinicaltrials gov. Identifier: NCT03770000).
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Linfoma de Células T Periférico , Linfoma de Células T , Neoplasias Cutâneas , Adulto , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Linfoma de Células T/tratamento farmacológico , Linfoma de Células T Periférico/tratamento farmacológico , Resultado do TratamentoRESUMO
Mycosis fungoides (MF) and Sézary Syndrome (SS) are the most common subtypes of cutaneous T cell lymphomas (CTCL). Advanced-stage MF/SS have poor prognoses and may be refractory to multiple systemic treatments. These cases can be difficult to achieve and maintain complete response and there is a need for novel therapeutics. Inhibition of the phosphatidylinositol 3-kinase (PI3K) pathway by Tenalisib presents one such emerging drug. We report a relapsed/refractory SS patient achieving complete remission using the combination of Tenalisib and Romidepsin and subsequently maintaining long-duration CR with Tenalisib monotherapy.
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Linfoma Cutâneo de Células T , Síndrome de Sézary , Neoplasias Cutâneas , Humanos , Síndrome de Sézary/tratamento farmacológico , Síndrome de Sézary/patologia , Fosfatidilinositol 3-Quinases , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Linfoma Cutâneo de Células T/tratamento farmacológicoRESUMO
Pulmonary leiomyoma has a diverse clinical spectrum of disease. Here we describe two patients with vastly different presentations. The first case is a 23-year-old female with a chronic cough and no visible tracheal lesion on computer tomography (CT) chest imaging. Flexible bronchoscopy revealed a small tracheal nodule, with histopathology confirming pulmonary leiomyoma. The second case is a 57-year-old female with a painless abdominal mass. CT imaging revealed widespread lung 'cannonball' nodules. Percutaneous biopsy confirmed metastatic leiomyoma. After progression on surveillance and endocrine therapy, she was commenced on doxorubicin with interval radiological improvement. These cases highlight the clinical heterogeneity in this disease, and thus, complexity in devising standardized diagnostic and therapeutic protocols.
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Dihydroorotate dehydrogenase (DHODH) is a mitochondrial enzyme that is essential for pyrimidine de novo synthesis. Rapidly growing cancer cells and replicating viruses are dependent on host cell nucleotides, the precursors of which are provided by DHODH. Hence, DHODH becomes an ideal target for pharmacological intervention. RP7214 is a potent and selective inhibitor of human DHODH and has shown antiviral and antileukaemic activity in preclinical studies. This paper describes the phase I study that evaluated the safety and pharmacokinetics of single and multiple ascending doses (SAD and MAD) and the food effect of RP7214 in healthy volunteers (HVs). The study was a randomized, double-blind, placebo-controlled trial of single dose (100, 200 and 400 mg QD), multiple doses (200 and 400 mg BID for 7 days) and a food effect study at a single dose of 200 mg. A total of 18, 12 and 12 HVs were enrolled in the SAD, MAD and food effect parts of the study, respectively. RP7214 was well tolerated at all dose levels. There were 20 treatment-emergent adverse events (TEAEs) reported, out of which most were mild to moderate in severity while three TEAEs were grade ≥3. RP7214 showed accumulation on multiple dosing. Steady-state concentrations were reached within about 3-6 days. The mean plasma half-life at steady-state was 12.8 hours (9.9-15.3). Food did not impact the absorption of RP7214. Inhibition of DHODH, as evidenced by increased dihydroorotate levels, was observed, confirming target engagement. The high systemic exposure with a favourable safety profile shows potential for the development of RP7214 in SARS-CoV-2 and acute myeloid leukaemia (NCT04680429).
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COVID-19 , Di-Hidro-Orotato Desidrogenase , Humanos , Voluntários Saudáveis , SARS-CoV-2 , Inibidores Enzimáticos/efeitos adversos , Método Duplo-Cego , Relação Dose-Resposta a DrogaRESUMO
WHAT IS KNOWN AND OBJECTIVE: RP3128, a novel, orally available modulator of calcium released activated calcium (CRAC) channel, is being developed for the potential treatment of autoimmune and inflammatory diseases. RP3128 showed nano-molar potency and activity in a range of in vitro and in vivo models of inflammation. We report a first-in-human study investigating the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of RP3128 in healthy subjects. METHODS: A randomized, double-blind, placebo-controlled trial of single (25, 50, 100, 200 and 400 mg) and multiple (7 days: 25, 100 and 400 mg once daily) doses of RP3128 were performed. Thirty-two and 24 subjects were randomized in the single ascending dose (SAD) and multiple ascending dose (MAD) parts, respectively. RESULTS AND DISCUSSION: RP3128 was well tolerated, with no dose-limiting toxicity at single and multiple doses. Incidence of treatment emergent adverse events (TEAEs) did not increase with ascending RP3128 doses. No changes were seen in cognitive function and ECG parameters. RP3128 was rapidly absorbed. Elimination was slow with a half-life of more than 80 h. Exposures increased with increasing doses. Accumulation was seen on repeated dosing. PD response, as evidenced by lower plasma levels of tumour necrosis factor-alfa (TNFα) and interleukin-4 (IL-4), was seen when compared to pre-dose values or placebo. WHAT IS NEW AND CONCLUSION: The safety, tolerability and PK/PD profile of RP3128 demonstrates its potential to be developed in inflammatory disorders and support further clinical development (ClinicalTrials.gov number: NCT02958982).
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Canais de Cálcio Ativados pela Liberação de Cálcio/antagonistas & inibidores , Compostos Orgânicos , Adolescente , Adulto , Doenças Autoimunes/tratamento farmacológico , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Interações Alimento-Droga , Meia-Vida , Voluntários Saudáveis , Humanos , Interleucina-4/sangue , Masculino , Pessoa de Meia-Idade , Compostos Orgânicos/administração & dosagem , Compostos Orgânicos/efeitos adversos , Compostos Orgânicos/farmacocinética , Fator de Necrose Tumoral alfa/sangue , Adulto JovemRESUMO
Tenalisib (RP6530), a dual phosphoinositide 3-kinase δ/γ inhibitor was evaluated in a phase I/Ib study for maximum tolerated dose (MTD), pharmacokinetics, and efficacy in patients with relapsed/refractory peripheral and cutaneous T-Cell Lymphoma (TCL). Histologically confirmed (TCL) patients, with ≥1 prior therapy received Tenalisib orally in a 28-day cycle in doses of 200 to 800 mg twice daily (800 mg in fasting and fed state) in escalation phase (n = 19) and 800 mg twice daily (fasting) in expansion phase (n = 39). The most frequently reported treatment emergent adverse events (TEAE) and related TEAE were fatigue (45%) and transaminase elevations (33%), respectively. Most frequently reported related Grade ≥3 TEAE was transaminase elevation (21%). Two dose-limiting toxicities occurred in the 800 mg fed cohort; hence, 800 mg fasting dose was deemed MTD. Tenalisib was absorbed rapidly with a median half-life of 2.28 h. Overall response rate in 35 evaluable patients was 45.7% (3 complete response (CR); 13 partial response (PR)) and median duration of response was 4.9 months. Responding tumors showed a marked downregulation of CD30, IL-31 and IL-32α. With an acceptable safety and promising clinical activity, Tenalisib can be a potential therapeutic option for relapsed/refractory TCL. Currently, a phase I/II combination study with romidepsin is ongoing.
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BACKGROUND: Tenalisib (RP6530) is a novel, highly specific, dual phosphoinositide-3 kinases (PI3K) δ/γ inhibitor with nano-molar potency. MATERIAL AND METHODS: This was a phase I, open-label, 3 + 3 dose escalation, maximum tolerated dose determination study to evaluate the safety, pharmacokinetics, and efficacy of tenalisib in patients with relapsed/refractory hematologic malignancies. Tenalisib was administered orally twice/thrice daily in 28-day cycles with starting dose of 25 mg twice daily. RESULTS: Thirty-five patients were enrolled across 11 dose levels. No dose limiting toxicity was reported at any of the dose levels. The most common treatment-emergent adverse events irrespective of causality were asthenia and cough in 15 (43%) patients and pyrexia in 13 (37%) patients. The most frequently reported related treatment-emergent adverse events were diarrhea, nausea, and vomiting. Related grade 3/4 adverse events were limited to events of hypertriglyceridemia, neutropenia, and diarrhea. Pharmacokinetics showed rapid absorption. Based on maximum plasma concentration and area under the plasma-concentration time curve, dose proportionality was observed up to 400 mg dose. Of 31 patients included in the efficacy analysis, complete response was seen in 2 (7%) patients and partial response in 4 (13%) patients, with an overall response rate of 19% and a disease-control rate of 61%. The median duration of response was 5.7 months. Responders demonstrated a marked downregulation of phospho-AKT on C1D8. CONCLUSION: Tenalisib demonstrated acceptable safety up to 1200 mg twice a day with no dose-limiting toxicities. Consistent clinical response was seen at doses 200 mg BID and above. Pharmacodynamics correlated well with clinical outcome. Further phase I/II studies are being undertaken to evaluate efficacy across different histologies.
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Benzopiranos/uso terapêutico , Neoplasias Hematológicas/tratamento farmacológico , Inibidores de Fosfoinositídeo-3 Quinase/uso terapêutico , Purinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Benzopiranos/farmacologia , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia , Purinas/farmacologia , Adulto JovemRESUMO
BACKGROUND: Australian National human immunodeficiency virus (HIV) Testing policy recommends HIV indicator condition-based testing, adapted from the European AIDS Clinical Society (EACS) guidelines. AIM: To evaluate the extent that Australian non-HIV specialty guidelines mention and recommend HIV testing in HIV indicator conditions. METHODS: EACS guidelines were reviewed to produce a list of 24 AIDS-defining conditions (ADC) and 31 indicator conditions (IC) where HIV prevalence >0.1%, and 5 IC where HIV non-diagnosis would have adverse effect on patients' management. Australian guidelines for these conditions were identified from websites of specialty societies, electronic Therapeutic Guidelines, National Health and Medical Research Council (NHMRC), state governments, MEDLINE and Google searches. We identified eight key IC as that were part of the HIDES I study. RESULTS: Overall, 51 ADC and IC had Australian guidelines: 24/51(47%) mention association with HIV and 14/51 (27%) recommend HIV testing. Twenty-five out of 51 (49%) Australian guidelines were for ADC: 18/25(72%) mention association with HIV and 5/25 (20%) recommend testing. Twenty-five out of 51 (49%) were guidelines IC with HIV prevalence of 0.1%: 6/25 (24%) mention HIV association and 8/25 (32%) recommend HIV testing. Two of eight (25%) key IC had no Australian guidelines and 3/8 (38%) do not mention HIV association or recommend HIV testing. CONCLUSIONS: Although almost half of HIV non-HIV guidelines for ADC and IC mention HIV association, only 27% specifically recommend HIV testing. This suggests partnership with guideline development and specialist groups may be useful to ensure patients diagnosed with ADC/IC are tested for HIV.
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Infecções por HIV , Medicina , Austrália/epidemiologia , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Teste de HIV , Humanos , PrevalênciaRESUMO
BACKGROUND: Conventional practice involves obtaining a blood culture during or immediately after a fever to increase diagnostic yield. There are no data to support this practice in children. METHODS: Retrospective single-center case-control study of children (0-18 years) who had blood cultures performed as part of routine care. Cases had an a priori defined pathogen isolated from blood culture (n = 410) and were age-matched with contemporaneous controls with a sterile blood culture (n = 410). The predictive value of fever (before and after blood culture), C-reactive protein and hematologic indices were analyzed by multivariate regression and area under the receiver operating characteristic curves (AUCs) in neonatal, general pediatric and pediatric oncology patients. RESULTS: One thousand one hundred seventy-two (6.7%) of 17,607 blood cultures were positive, of which 410 (35%) cultured pathogen(s). Three hundred and twenty four (79%) cases and 275 (67.1%) controls had a fever (≥37.5°C) during the 12 hours pre- or post-collection. Fever 2-6 hours before a blood culture was neither sensitive nor specific for predicting bacteremia in neonatal or pediatric patients and marginally predictive in oncology patients (AUC 0.59-0.63). Cultures obtained 2-6 hours before fever were nonpredictive in neonates (AUC 0.56-0.59), marginally predictive in pediatric patients (AUC 0.64-0.67) and moderately predictive in oncology patients (AUC 0.70). C-reactive protein was marginally predictive in neonates (AUC 0.60). Hematologic indices were nonpredictive in all groups. CONCLUSIONS: Fever before obtaining blood culture was neither sensitive nor specific for culture positivity; timing of pediatric blood cultures relative to fever is unimportant. Bacteremia precedes a fever, but this is of limited clinical applicability.
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Bacteriemia/diagnóstico , Hemocultura/métodos , Coleta de Amostras Sanguíneas/métodos , Febre/diagnóstico , Adolescente , Bacteriemia/complicações , Bacteriemia/epidemiologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Febre/etiologia , Humanos , Lactente , Recém-Nascido , Curva ROC , Estudos Retrospectivos , Fatores de TempoRESUMO
The best management of infected fluid collections depends on a careful assessment of clinical and anatomic factors as well as an up-to-date review of the published literature, to be able to select from a host of multidisciplinary treatment options. This article reviews conservative, radiologic, endoscopic, and surgical options and their best application to infected fluid collections as determined by the ACR Appropriateness Criteria Expert Panel on Interventional Radiology. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every three years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals, and the application, by the panel, of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
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Abscesso/terapia , Drenagem/normas , Endoscopia/normas , Guias de Prática Clínica como Assunto , Radiografia Intervencionista/normas , Radiologia/normas , Abscesso/diagnóstico por imagem , Humanos , Estados UnidosRESUMO
AIM: The present study was conducted to investigate the effect of species, breed and age on bacterial load in fresh and frozen semen of Cattle and Buffalo bull. MATERIALS AND METHODS: Present study covered 56 cow and 10 buffalo bulls stationed at Central Semen Station Anjora, Durg (Chhattisgarh). Impact of breeds on bacterial load in semen was assessed using six breeds of cattle viz. Sahiwal, Gir, Red Sindhi, Tharparkar, Jersey and Holstein Friesian (HF) cross. Cow bulls were categorized into four different groups based on their age (<4 years, 4-5 years, 5-6 years and > 6 years) to study variation among age groups. Bacterial load was measured in fresh and frozen semen samples from these bulls using the standard plate count (SPC) method and count was expressed as colony forming unit (CFU) per ml of semen. RESULTS: Higher bacterial load was reported in fresh (2.36 × 10(4) ± 1943 CFU/ml) and frozen (1.00 × 10 ± 90 CFU/ml) semen of cow bulls as compared to buffalo bulls (1.95 × 10(4) ± 2882 and 7.75 × 10(2) ± 160 CFU/ml in fresh and frozen semen, respectively). Jersey bull showed significantly higher bacterial count (p < 0.05) both in fresh (4.07 × 10(4) ± 13927 CFU/ml) and frozen (1.92 × 10(3) ± 178 CFU/ml) semen followed by HF cross, Sahiwal, Gir, Red Sindhi and Tharparkar bull. Bulls aged < 4 years and more than 6 years yielded increased bacterial load in their semen. Although a minor variation was reported between species and among age groups, no significant differences were measured. CONCLUSION: Bacterial load in semen did not differ significantly between species and age groups; however significant variation was reported among different breeds. Bulls of Jersey breed showed significantly higher bacterial load in semen as compared to the crossbred and indigenous bull.
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AIM: The present investigation was conducted to locate the critical sources of bacterial contamination and to evaluate the standard sanitation protocol so as to improve the hygienic conditions during collection, evaluation, and processing of bull semen in the Semen Station. MATERIALS AND METHODS: The study compared two different hygienic procedures during the collection, evaluation and processing of semen in Central Semen Station, Anjora, Durg. Routinely used materials including artificial vagina (AV) inner liner, cone, semen collection tube, buffer, extender/diluter, straws; and the laboratory environment like processing lab, pass box and laminar air flow (LAF) cabinet of extender preparation lab, processing lab, sealing filling machine, and bacteriological lab were subjected to bacteriological examination in two phases of study using two different sanitary protocols. Bacterial load in above items/environment was measured using standard plate count method and expressed as colony forming unit (CFU). RESULTS: Bacterial load in a laboratory environment and AV equipments during two different sanitary protocol in present investigation differed highly significantly (p<0.001). Potential sources of bacterial contamination during semen collection and processing included laboratory environment like processing lab, pass box, and LAF cabinets; AV equipments, including AV Liner and cone. Bacterial load was reduced highly significantly (p<0.001) in AV liner (from 2.33±0.67 to 0.50±0.52), cone (from 4.16±1.20 to 1.91±0.55), and extender (from 1.33±0.38 to 0) after application of improved practices of packaging, handling, and sterilization in Phase II of study. Glasswares, buffers, and straws showed nil bacterial contamination in both the phases of study. With slight modification in fumigation protocol (formalin @600 ml/1000 ft(3)), bacterial load was significantly decreased (p<0.001) up to 0-6 CFU in processing lab (from 6.43±1.34 to 2.86±0.59), pass box (from 12.13±2.53 to 3.78±0.79), and nil bacterial load was reported in LAFs. CONCLUSION: Appropriate and careful management considering critical points step by step starting right from collection of semen to their processing can significantly minimize bacterial contamination.
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The optimal treatment for patients with biliary obstruction varies depending on the underlying cause of the obstruction, the clinical condition of the patient, and anticipated long-term effects of the procedure performed. Endoscopic and image-guided procedures are usually the initial procedures performed for biliary obstructions. Various options are available for both the radiologist and endoscopist, and each should be considered for any individual patient with biliary obstruction. This article provides an overview of the current status of radiologic procedures performed in the setting of biliary obstruction and describes multiple clinical scenarios that may be treated by radiologic or other methods. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
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Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/terapia , Colestase/diagnóstico , Colestase/terapia , Diagnóstico por Imagem/normas , Descompressão Cirúrgica , Drenagem , Endoscopia do Sistema Digestório , Medicina Baseada em Evidências/normas , Humanos , Radiologia Intervencionista/normas , StentsRESUMO
Management of hepatic malignancy is a challenging clinical problem involving several different medical and surgical disciplines. Because of the wide variety of potential therapies, treatment protocols for various malignancies continue to evolve. Consequently, development of appropriate therapeutic algorithms necessitates consideration of medical options, such as systemic chemotherapy; surgical options, such as resection or transplantation; and locoregional therapies, such as thermal ablation and transarterial embolization. The authors discuss treatment strategies for the 3 most common subtypes of hepatic malignancy treated with locoregional therapies: hepatocellular carcinoma, neuroendocrine metastases, and colorectal metastases. The ACR Appropriateness Criteria(®) are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
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Diagnóstico por Imagem/normas , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Oncologia/normas , Guias de Prática Clínica como Assunto , Radiologia/normas , Humanos , Estados UnidosRESUMO
Pulmonary and mediastinal masses represent a wide range of pathologic processes with very different treatment options. Although advances in imaging (such as PET and high-resolution CT) help in many cases with the differential diagnosis of thoracic pathology, tissue samples are frequently needed to determine the best management for patients presenting with thoracic masses. There are many options for obtaining tissue samples, each of which has its own set of benefits and drawbacks. The purposes of this report are to present the most current evidence regarding biopsies of thoracic nodules and masses and to present the most appropriate options for select common clinical scenarios. The ACR Appropriateness Criteria(®) are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
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Diagnóstico por Imagem , Neoplasias Pulmonares/diagnóstico , Doenças Torácicas/diagnóstico , Biópsia/métodos , Técnica Delphi , Diagnóstico Diferencial , Medicina Baseada em Evidências , Humanos , Doenças do Mediastino/diagnóstico , Radiografia IntervencionistaRESUMO
Hepatic abscess following transarterial chemoembolization is an uncommon complication. The authors describe a case of liver abscess after transarterial chemoembolization for neuroendocrine liver metastases, including risk factors, prophylaxis, treatment, and outcomes.
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Nontarget embolization during transarterial chemoembolization, although infrequent, can be a serious complication. The authors describe a case of nontarget gastric embolization to the stomach after transarterial chemoembolization and describe the published incidence of nontarget embolization to various organs, its diagnosis, treatment, and possible outcomes.
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The soft X-ray microscope at the Lawrence Berkeley National Laboratory was developed for visualization of biological tissue. Soft X-ray microscopy provides high-resolution visualization of hydrated, non-embedded and non-sectioned cells and is thus potentially an alternative to transmission electron microscopy. Here we show for the first time soft X-ray micrographs of structures isolated from the guinea-pig inner ear. Sensory outer hair cells and supporting pillar cells are readily visualized. In the hair cells, individual stereocilia can easily be identified within the apical hair bundle. The underlying cuticular plate is, however, too densely composed or too thick to be clearly visualized, and thus appears very dark. The cytoplasmic structures protruding from the cuticular plates as well as the fibrillar material surrounding and projecting from the cell nuclei can be seen. In the pillar cells the images reveal individual microtubule bundles. Soft X-ray images of the acellular tectorial membrane and thin two-layered Reissner's membrane display a level of resolution comparable to low-power electron microscopy.
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Orelha Interna/anatomia & histologia , Frações Subcelulares/ultraestrutura , Animais , Orelha Interna/fisiologia , Orelha Interna/ultraestrutura , Microanálise por Sonda Eletrônica/métodos , Cobaias , Audição/fisiologia , Processamento de Imagem Assistida por Computador , Frações Subcelulares/fisiologiaRESUMO
OBJECTIVE: Endoscopic third ventriculostomy has developed into a therapeutic alternative to shunting for the management of carefully selected patients with primarily noncommunicating hydrocephalus. This procedure, however, requires a general anesthetic and necessitates violation of the brain parenchyma and manipulation near vital neural structures to access the floor of the third ventricle. Using two cadavers and off-the-shelf angiographic catheters, we sought to determine whether it was possible to navigate a catheter, angioplasty balloon, and stent percutaneously through the subarachnoid space from the thecal sac into the third ventricle so as to perform a third ventriculostomy from below. METHODS: Using biplane angiography and off-the-shelf angiographic catheters along with angioplasty balloons and stents, we were able to pass a stent coaxially from the thecal sac to and across the floor of the third ventricle so as to achieve a third ventriculostomy from below. RESULTS: Coaxial catheter techniques allowed for the percutaneous insertion of a stent across the floor of the third ventricle. Ventriculostomy was confirmed by injecting contrast medium into the lateral ventricle and seeing it pass through the stent and into the chiasmatic cistern. CONCLUSION: We describe the performance of third ventriculostomies in two cadavers by use of the new concept of percutaneous intradural neuronavigation. This procedure may obviate the need for general anesthetic and minimize the potential for brain and vascular injury, especially if ultimately combined with magnetic resonance fluoroscopy.