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BACKGROUND: 6-mercaptopurine is a cornerstone of maintenance therapy for pediatric ALL. Response to 6MP is typically determined by the ANC. Therapeutic ANC range while receiving 6MP is between 500 and 1500/µL. In addition to desired myelosuppression, 6MP is associated with multiple adverse drug effects. Increased doses of 6MP can lead to therapeutic ANC values; however, patients may experience adverse effects before obtaining therapeutic myelosuppression, often deemed "skewed metabolism." Allopurinol may potentially correct skewed 6MP metabolism. PROCEDURE: Pediatric patients with ALL with 6MMP and 6TGN metabolites drawn during maintenance therapy were analyzed for allopurinol use. The primary outcome evaluated the percentage of time spent in therapeutic ANC range before and after allopurinol initiation. In addition, the difference in 6MMP:6TGN ratios before and after allopurinol initiation, incidence of hepatotoxicity, and rates of relapse, were analyzed. RESULTS: Ninety-five patients were included for analysis. Thirty-two (34%) patients received allopurinol. There were no significant differences in baseline demographics between the patients who received allopurinol and those who did not. When comparing ANC values pre- and post-allopurinol initiation, a statistically significant increase in the percentage of time spent in therapeutic range was observed (27% vs. 43%; p = .03). In addition, when comparing metabolite ratios pre- and post-allopurinol initiation, a statistically significant decrease in 6MMP:6TGN metabolite ratio values was observed (86.7 vs. 3.6; p < .0001). CONCLUSIONS: Allopurinol significantly increased the percent time in therapeutic ANC range and can be safely utilized to significantly lower the ratio of 6MMP:6TGN metabolites, alleviating the undesirable side effects of 6MMP, and optimizing the anti-leukemic effects associated with 6TGN.
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Aims: We aimed to identify the distinctive cardiovascular magnetic resonance (CMR) features of patients with left bundle branch block (LBBB) and heart failure with reduced ejection fraction (HFrEF) of presumed non-ischaemic aetiology. The secondary aim was to determine whether these individuals exhibit characteristics that could potentially serve as predictors of left ventricular ejection fraction (LVEF) recovery as compared with patients without LBBB. Methods and results: We prospectively recruited patients with HFrEF (LVEF ≤ 40%) on echocardiography who were referred for early CMR examination. Patients with an established diagnosis of coronary artery disease and known structural or congenital heart disease were excluded. LV recovery was defined as achieving ≥10% absolute improvement to ≥40% in LVEF between baseline evaluation to CMR. A total of 391 patients were recruited including 115 (29.4%) with LBBB. Compared with HF patients without LBBB, those with LBBB exhibited larger left ventricles and smaller right ventricles, but no differences were observed with respect to LVEF (35.8 ± 12 vs. 38 ± 12%, P = 0.105). The overall rate of LV recovery from baseline echocardiogram to CMR (70 [42-128] days) was not significantly different between LBBB and non-LBBB patients (27.8% vs. 31.5%, P = 0.47). Reduced LVEF remained an independent predictor of LV non-recovery only in patients with LBBB. Conclusion: Patients presenting with HFrEF and LBBB had larger LV cavities and smaller RV cavities than those without LBBB but no difference in prevalence of scar or ischaemia. The rates of LV recovery were similar between both groups, which supports current guidelines to defer device therapy until 3-6 months of guideline-directed medical therapy, rather than early CMR and device implantation.
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BACKGROUND: Whole blood (WB) collections can occur downrange for immediate administration. An important aspect of these collections is determining when the unit is sufficiently full. This project tested a novel method for determining when a field collection is complete. METHODS: The amount of empty space at the top of WB units, destined to become LTOWB or separated into components, that were collected at blood centers or hospitals was measured by holding a WB unit off the ground and placing the top of a piece of string where the donor tubing entered the bag. The string was marked where it intersected the top of the column of blood in the bag and measured from the top. The WB units were also weighed. RESULTS: A total of 15 different bags, two of which were measured in two different filling volumes, from 15 hospitals or blood centers were measured and weighed. The most commonly used blood bag, Terumo Imuflex SP, had a median string length of 9 mm (range: 2-24 mm) and weighed a median of 565.1 g (range: 524.8-636.7 g). CONCLUSION: Pieces of string can be precut to the appropriate length depending on the type of bag before a mission where field WB collections might be required and a mark placed on the bag before the collection commences to indicate when the unit is full.
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Doadores de Sangue , Humanos , Bancos de Sangue , Coleta de Amostras Sanguíneas/métodos , Coleta de Amostras Sanguíneas/instrumentaçãoRESUMO
Although genome-wide association studies (GWAS) have successfully linked genetic risk loci to various disorders, identifying underlying cellular biological mechanisms remains challenging due to the complex nature of common diseases. We established a framework using human peripheral blood cells, physical, chemical and pharmacological perturbations, and flow cytometry-based functional readouts to reveal latent cellular processes and performed GWAS based on these evoked traits in up to 2,600 individuals. We identified 119 genomic loci implicating 96 genes associated with these cellular responses and discovered associations between evoked blood phenotypes and subsets of common diseases. We found a population of pro-inflammatory anti-apoptotic neutrophils prevalent in individuals with specific subsets of cardiometabolic disease. Multigenic models based on this trait predicted the risk of developing chronic kidney disease in type 2 diabetes patients. By expanding the phenotypic space for human genetic studies, we could identify variants associated with large effect response differences, stratify patients and efficiently characterize the underlying biology.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/genética , Estudo de Associação Genômica Ampla , Locos de Características Quantitativas/genética , Predisposição Genética para Doença , Fenótipo , Células Sanguíneas , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
BACKGROUND: As radiation therapy (RT) for Wilms tumor (WT) evolves with more conformal techniques, it is necessary to evaluate patterns of failure and toxicity. We sought to determine the rate of local failure (LF) after abdominal RT in WT, specifically focusing on those with contained rupture treated with whole abdominal and pelvic RT (WAPRT) vs flank RT. Secondary objectives were to determine overall survival (OS), distant failure (DF), and late toxicities. METHODS: A single institution retrospective study of 54 pediatric patients with WT treated with abdominal RT between May 2000 and October 2022. LF and DF were calculated through cumulative incidence function and OS by Kaplan-Meier method. RESULTS: The median age was 4.5 years and the median follow-up was 6 years. Most patients (91%) had favorable histology. Only 1 patient experienced LF, 15 months from completion of RT (cumulative incidence 2% at 5 y). All patients who received unilateral flank radiation for contained rupture/spillage (n=13) experienced long-lasting intra-abdominal tumor control. A total of 5 patients experienced a DF at a median of 7 months, all in the lung. No patient relapsed in the lungs after upfront whole lung irradiation (n=16). OS was 96% at 5 years. Among 28 patients who followed through puberty, 4 female patients with prior WAPRT experienced hormonal irregularities/infertility. CONCLUSIONS: Unilateral flank radiation may be a viable alternative to WAPRT for contained rupture/spillage and should be further explored prospectively. Our results may also be utilized in the future for outcome and toxicity comparison as conformal radiation techniques evolve.
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Neoplasias Renais , Radioterapia Conformacional , Tumor de Wilms , Humanos , Criança , Feminino , Pré-Escolar , Estudos Retrospectivos , Tumor de Wilms/radioterapia , Radioterapia Conformacional/efeitos adversos , Tórax , Neoplasias Renais/radioterapiaRESUMO
GM2 gangliosidoses are a group of neurodegenerative lysosomal storage disorders that are characterized by the accumulation of GM2 gangliosides (GM2), leading to rapid neurological decline and death. The hydrolysis of GM2 requires the specific synthesis, processing, and combination of products of three genes-HEXA, HEXB, and GM2A-within the cell's lysosomes. Mutations in these genes result in Tay-Sachs disease, Sandhoff disease, or AB-variant GM2 gangliosidosis (ABGM2), respectively. ABGM2, the rarest of the three types, is characterized by a mutation in the GM2A gene, which encodes the GM2 activator (GM2A) protein. Being a monogenic disease, gene therapy is a plausible and likely effective method of treatment for ABGM2. This study aimed at assessing the effects of administering a one-time intravenous treatment of single-stranded Adeno-associated virus serotype 9 (ssAAV9)-GM2A viral vector at a dose of 1 × 1014 vector genomes (vg) per kilogram per mouse in an ABGM2 mouse model (Gm2a-/-). ssAAV9-GM2A was administered at 1-day (neonatal) or 6-weeks of age (adult-stage). The results demonstrated that, in comparison to Gm2a-/- mice that received a vehicle injection, the treated mice had reduced GM2 accumulation within the central nervous system and had long-term persistence of vector genomes in the brain and liver. This proof-of-concept study is a step forward towards the development of a clinically therapeutic approach for the treatment of patients with ABGM2.
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Gangliosidoses GM2 , Doença de Tay-Sachs , Humanos , Animais , Camundongos , Dependovirus/genética , Sorogrupo , Doença de Tay-Sachs/terapia , Gangliosidoses GM2/genética , Gangliosidoses GM2/terapia , Proteína Ativadora de G(M2)/genética , Terapia GenéticaRESUMO
BACKGROUND: Infantile myofibromatosis (IM) is a rare benign tumor of infancy. Cases with solitary and multicentric disease usually spontaneously regress, but multicentric disease with visceral involvement carries a poor prognosis. Few cases of multicentric disease with central nervous system (CNS) involvement have been reported, and none report survival. OBSERVATIONS: We present a newborn with multicentric IM with cutaneous, visceral, and CNS involvement. She was treated with vinblastine, methotrexate, and the novel addition of intrathecal methotrexate with treatment response after 1 year of therapy. CONCLUSIONS: Multicentric IM with CNS involvement can be successfully treated with a multimodal approach of chemotherapy with the addition of intrathecal methotrexate and surgery.
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Metotrexato , Miofibromatose , Recém-Nascido , Feminino , Humanos , Metotrexato/uso terapêutico , Miofibromatose/terapia , Miofibromatose/patologia , Vimblastina/uso terapêuticoRESUMO
In the coming decades, warming and deoxygenation of marine waters are anticipated to result in shifts in the distribution and abundance of fishes, with consequences for the diversity and composition of fish communities. Here, we combine fisheries-independent trawl survey data spanning the west coast of the USA and Canada with high-resolution regional ocean models to make projections of how 34 groundfish species will be impacted by changes in temperature and oxygen in British Columbia (BC) and Washington. In this region, species that are projected to decrease in occurrence are roughly balanced by those that are projected to increase, resulting in considerable compositional turnover. Many, but not all, species are projected to shift to deeper depths as conditions warm, but low oxygen will limit how deep they can go. Thus, biodiversity will likely decrease in the shallowest waters (less than 100 m), where warming will be greatest, increase at mid-depths (100-600 m) as shallow species shift deeper, and decrease at depths where oxygen is limited (greater than 600 m). These results highlight the critical importance of accounting for the joint role of temperature, oxygen and depth when projecting the impacts of climate change on marine biodiversity. This article is part of the theme issue 'Detecting and attributing the causes of biodiversity change: needs, gaps and solutions'.
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Biodiversidade , Oxigênio , Animais , Peixes , Mudança Climática , Canadá , EcossistemaRESUMO
BACKGROUND: Shock index (SI) equals the ratio of heart rate (HR) to systolic blood pressure (SBP) with clinical evidence that it is more sensitive for trauma patient status assessment and prediction of outcome compared with either HR or SBP alone. We used lower body negative pressure (LBNP) as a human model of central hypovolemia and compensatory reserve measurement (CRM) validated for accurate tracking of reduced central blood volume to test the hypotheses that SI: (1) presents a late signal of central blood volume status; (2) displays poor sensitivity and specificity for predicting the onset of hemodynamic decompensation; and (3) cannot identify individuals at greatest risk for the onset of circulatory shock. METHODS: We measured HR, SBP, and CRM in 172 human subjects (19-55 years) during progressive LBNP designed to determine tolerance to central hypovolemia as a model of hemorrhage. Subjects were subsequently divided into those with high tolerance (HT) (n = 118) and low tolerance (LT) (n = 54) based on completion of 60 mm Hg LBNP. The time course relationship between SI and CRM was determined and receiver operating characteristic (ROC) area under the curve (AUC) was calculated for sensitivity and specificity of CRM and SI to predict hemodynamic decompensation using clinically defined thresholds of 40% for CRM and 0.9 for SI. RESULTS: The time and level of LBNP required to reach a SI = 0.9 (~60 mm Hg LBNP) was significantly greater ( p < 0.001) compared with CRM that reached 40% at ~40 mm Hg LBNP. Shock index did not differ between HT and LT subjects at 45 mm Hg LBNP levels. ROC AUC for CRM was 0.95 (95% CI = 0.94-0.97) compared with 0.91 (0.89-0.94) for SI ( p = 0.0002). CONCLUSION: Despite high sensitivity and specificity, SI delays time to detect reductions in central blood volume with failure to distinguish individuals with varying tolerances to central hypovolemia. LEVEL OF EVIDENCE: Diagnostic Test or Criteria; Level III.
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Hemodinâmica , Hipovolemia , Humanos , Hipovolemia/diagnóstico , Hemodinâmica/fisiologia , Volume Sanguíneo/fisiologia , Pressão Sanguínea/fisiologia , Frequência Cardíaca/fisiologia , Pressão Negativa da Região Corporal InferiorRESUMO
BACKGROUND: Survival for children with metastatic hepatoblastoma (HB) remains suboptimal. We report the response rate and outcome of two courses of vincristine/irinotecan/temsirolimus (VIT) in children with high-risk (HR)/metastatic HB. PROCEDURES: Patients with newly diagnosed HB received HR window chemotherapy if they had metastatic disease or a serum alpha-fetoprotein (AFP) level less than 100 ng/mL. Patients received vincristine (days 1 and 8), irinotecan (days 1-5), and temsirolimus (days 1 and 8). Cycles were repeated every 21 days. Responders had either a 30% decrease using RECIST (Response Evaluation Criteria in Solid Tumors) criteria OR a 90% (>1 log10 decline) AFP decline after two cycles. Responders received two additional cycles of VIT intermixed with six cycles of cisplatin/doxorubicin/5-fluorouracil/vincristine (C5VD). Nonresponders received six cycles of C5VD alone. RESULTS: Thirty-six eligible patients enrolled on study. The median age at enrollment was 27 months (range: 7-170). Seventeen of 36 patients were responders (RECIST and AFP = 3, RECIST only = 4, AFP only = 10). The median AFP at diagnosis was 222,648 ng/mL and the median AFP following two VIT cycles was 19,262 ng/mL. Three-year event-free survival was 47% (95% confidence interval [CI]: 30%-62%), while overall survival was 67% (95% CI: 49%-80%). CONCLUSION: VIT did not achieve the study efficacy endpoint. Temsirolimus does not improve the response rate seen in patients treated with vincristine and irinotecan (VI) alone as part of the initial treatment regimen explored in this study. Additionally, AFP response may be a more sensitive predictor of disease response than RECIST in HB.
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Hepatoblastoma , Neoplasias Hepáticas , Criança , Humanos , Hepatoblastoma/patologia , Irinotecano/uso terapêutico , Vincristina , Neoplasias Hepáticas/patologia , alfa-Fetoproteínas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resultado do TratamentoRESUMO
INTRODUCTION: Tension pneumothorax (TPX) is the third most common cause of preventable death in trauma. Needle decompression at the fifth intercostal space at anterior axillary line (5th ICS AAL) is recommended by Tactical Combat Casualty Care (TCCC) with an 83-mm needle catheter unit (NCU). We sought to determine the risk of cardiac injury at this site. METHODS: Institutional data sets from two trauma centers were queried for 200 patients with CT chest. Inclusion criteria include body mass index of =30 and age 18-40 years. Measurements were taken at 2nd ICS mid clavicular line (MCL), 5th ICS AAL and distance from the skin to pericardium at 5th ICS AAL. Groups were compared using Mann-Whitney U and chi-squared tests. RESULTS: The median age was 27 years with median BMI of 23.8 kg/m2. The cohort was 69.5% male. Mean chest wall thickness at 2nd ICS MCL was 38-mm (interquartile range (IQR) 32-45). At 5th ICS AAL, the median chest wall thickness was 30-mm (IQR 21-40) and the distance from skin to pericardium was 66-mm (IQR 54-79). CONCLUSION: The distance from skin to pericardium for 75% of patients falls within the length of the recommended needle catheter unit (83-mm). The current TCCC recommendation to "hub" the 83mm needle catheter unit has potential risk of cardiac injury.
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Pneumotórax , Humanos , Masculino , Adulto , Adolescente , Adulto Jovem , Feminino , Pneumotórax/etiologia , Pneumotórax/terapia , Toracostomia/efeitos adversos , Descompressão Cirúrgica/efeitos adversos , Catéteres/efeitos adversos , Agulhas/efeitos adversosRESUMO
INTRODUCTION: Limb and junctional hemorrhage are leading causes of potentially preventable death among trauma casualties. Hemorrhage control for these regions could be achieved by direct or indirect pressure. The manual pressure points (MPP) involves applying manual pressure on the arterial supply to occlude distal blood flow without the need for specialized equipment. STUDY DESIGN AND METHODS: Prospective, non-randomized, human volunteer, controlled environment study involving 38 healthy military caregivers, with 26 participants attending a short instructional session. During a medical exercise, participants were requested to apply pressure on the supraclavicular and femoral points aiming to stop regional blood flow, measured by distal pulse palpation. The measures recorded included achievement of distal pulse cessation, success in achieving cessation for a full minute, and subjects' pain scores reported after each attempt. RESULTS: All participants succeeded in achieving distal pulse cessation for both the supraclavicular and femoral points for a full minute. The median time to initial success was 3.0 (interquartile range 2.0-5.0) seconds in the supraclavicular point and 4.5 (interquartile range 3.0-6.0) seconds in the femoral point. Pain scores ranging between 0 and 3 were reported by most subjects during supraclavicular (68.4%) and femoral occlusion (84.2%). CONCLUSION: The MPP technique was highly effective in occluding distal palpable pulses in healthy volunteers when applied to the supraclavicular and femoral arteries. Brief instruction on the technique can potentially improve the chances of achieving hemorrhage control within 5 s. Further research is required to determine efficacy among different populations and providers with varying experience levels.
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Hemodinâmica , Hemorragia , Humanos , Estudos Prospectivos , Hemorragia/etiologia , Artéria Femoral/lesões , DorRESUMO
BACKGROUND: Patients with relapsed and refractory solid and central nervous system (CNS) tumors have poor outcomes and need novel therapeutic options. Vincristine, irinotecan, and temozolomide (VIT) is a common chemotherapy regimen in relapsed pediatric tumors with an established toxicity profile. Metformin shows preclinical anti-cancer activity through multiple pathways. METHODS: The objective of this Phase I trial was to establish the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) of metformin in combination with VIT in children with relapsed and refractory solid and CNS tumors. A 3 + 3 design was used to test the addition of metformin at five dose levels (666, 999, 1333, 1666, and 2000 mg/m2 /day). Therapy toxicity, pharmacokinetics, and radiologic response to treatment were evaluated. RESULTS: Twenty-six patients (median age 13 years, range 2-18 years) were enrolled with 22 evaluable for toxicity. The most common diagnoses were Ewing sarcoma (n = 8), rhabdomyosarcoma (n = 3) and atypical teratoid/rhabdoid tumor (n = 3). The MTD was exceeded at Dose Level 5 due to two dose-limiting toxicities; both were Grade 3 diarrhea requiring prolonged hospitalization and intravenous fluids. The MTD was not determined due to study closure with less than six patients enrolled at Dose Level 4. Frequently observed toxicities were gastrointestinal (most notably diarrhea) and hematologic. Amongst 16 patients evaluable for best overall response, there was one complete response (Ewing sarcoma), three partial responses (Ewing sarcoma, glioblastoma multiforme, and alveolar rhabdomyosarcoma), and five patients with stable disease. CONCLUSIONS: The MTD of VIT with metformin was not determined due to premature study closure. We recommend an RP2D of Dose Level 4, 1666 mg/m2 /day. Radiographic responses were seen in multiple tumor types. Further evaluation for efficacy could be investigated in a Phase II trial.
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Neoplasias do Sistema Nervoso Central , Metformina , Neoplasias , Sarcoma de Ewing , Criança , Humanos , Pré-Escolar , Adolescente , Irinotecano/efeitos adversos , Temozolomida/uso terapêutico , Vincristina/uso terapêutico , Sarcoma de Ewing/tratamento farmacológico , Metformina/uso terapêutico , Camptotecina , Dacarbazina , Neoplasias/tratamento farmacológico , Neoplasias/etiologia , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Dose Máxima Tolerável , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Recidiva Local de Neoplasia/tratamento farmacológicoRESUMO
OBJECTIVE: Practice patterns and durability of parallel stent graft techniques in complex endovascular aneurysm repair (EVAR) remain poorly defined. We aimed to quantify and compare the impact of renal chimney intra-aortic stent length (IASL) on geometric deformations of renal arteries in complex EVAR. METHODS: Thirty-eight nonconsecutive patients underwent EVAR utilizing parallel stent graft techniques (chimney EVAR [chEVAR], n = 28; chimney endovascular aneurysm sealing [chEVAS], n = 10) between 2010 and 2016. A total of 59 renal chimney stent grafts were used. Geometric quantification was derived from three-dimensional model-based centerline extraction. Renal chimney intra-aortic stent length (IASL) was defined as the length of chimney stent that extended from the proximal edge of the chimney stent to the ostium of the corresponding renal artery. RESULTS: Mean IASL for both left and right renal arteries in the cohort was 35.7 mm. Renal arteries containing chimney IASL <30 mm trended toward a greater branch angle (135.4 vs. 127.8°, p = .06). Left renal arteries showed significantly greater branch angle among those with IASL <40 mm (135.5 vs. 121.7°, p = .045). Mean IASL for renal arteries in chEVAR was significantly longer compared to chEVAS (39.2 vs. 26.3 mm, p = .003). No difference was noted in overall branch angle or end-stent angle based on procedure type. ChEVAR with IASL <30 mm had significantly greater end-stent angle (48.2 vs. 33.5°, p = .03). In contrast, chEVAS patients showed no difference in end-stent angle based on IASL thresholds, but did have significantly greater branch angle among those with IASL <30 mm when grouped by both all renal arteries (133.5 vs. 113.5°, p = .004) and right renal arteries (134.3 vs. 111.6°, p = .02). CONCLUSIONS: Renal chimney stents with longer IASL appear to exhibit less renal artery deformation, suggesting a more gradual and perpendicular transition of the chimney stent across the renal ostium.
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Aneurisma da Aorta Abdominal , Implante de Prótese Vascular , Procedimentos Endovasculares , Humanos , Prótese Vascular , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/métodos , Correção Endovascular de Aneurisma , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/cirurgia , Resultado do Tratamento , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/métodos , Aortografia/métodos , Stents , Desenho de PróteseRESUMO
Immunomodulatory (IM) metabolic reprogramming in macrophages (MÏs) is fundamental to immune function. However, limited information is available for human MÏs, particularly in response plasticity, which is critical to understanding the variable efficacy of immunotherapies in cancer patients. We carried out an in-depth analysis by combining multiplex stable isotope-resolved metabolomics with reversed phase protein array to map the dynamic changes of the IM metabolic network and key protein regulators in four human donors' MÏs in response to differential polarization and M1 repolarizer ß-glucan (whole glucan particles [WGPs]). These responses were compared with those of WGP-treated ex vivo organotypic tissue cultures (OTCs) of human non-small cell lung cancer. We found consistently enhanced tryptophan catabolism with blocked NAD+ and UTP synthesis in M1-type MÏs (M1-MÏs), which was associated with immune activation evidenced by increased release of IL-1ß/CXCL10/IFN-γ/TNF-α and reduced phagocytosis. In M2a-MÏs, WGP treatment of M2a-MÏs robustly increased glucose utilization via the glycolysis/oxidative branch of the pentose phosphate pathway while enhancing UDP-N-acetyl-glucosamine turnover and glutamine-fueled gluconeogenesis, which was accompanied by the release of proinflammatory IL-1ß/TNF-α to above M1-MÏ's levels, anti-inflammatory IL-10 to above M2a-MÏ's levels, and attenuated phagocytosis. These IM metabolic responses could underlie the opposing effects of WGP, i.e., reverting M2- to M1-type immune functions but also boosting anti-inflammation. Variable reprogrammed Krebs cycle and glutamine-fueled synthesis of UTP in WGP-treated OTCs of human non-small cell lung cancer were observed, reflecting variable M1 repolarization of tumor-associated MÏs. This was supported by correlation with IL-1ß/TNF-α release and compromised tumor status, making patient-derived OTCs unique models for studying variable immunotherapeutic efficacy in cancer patients.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , beta-Glucanas , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Glucosamina/metabolismo , Glucose/metabolismo , Glutamina/metabolismo , Humanos , Interleucina-10 , Neoplasias Pulmonares/metabolismo , Macrófagos , NAD/metabolismo , Fagocitose , Triptofano/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Difosfato de Uridina/metabolismo , Uridina Trifosfato/metabolismo , beta-Glucanas/metabolismoRESUMO
Spontaneous coronary artery dissection (SCAD) is a less common cause of acute coronary syndrome. Pregnancy-related SCAD is uncommon, but often presents with a more severe phenotype. This report describes a 30-year-old woman with an anterior ST elevation MI, presenting 1 day postpartum. Left main stem (LMS) SCAD with extensive intramural haematoma (IMH) and resultant LMS occlusion was confirmed by angiography and intravascular imaging. Given the extent of disease, the patient underwent emergency cardiac surgery. Coronary flow was initially improved by decompressing the IMH using cutting balloons. The coronary wires were successfully left in situ during transfer in an effort to both maintain flow and allow the surgeon to identify true LMS. Ideally, SCAD can be managed conservatively given the risk of intervention worsening IMH, and hence myocardial ischaemia/MI. However, emergency revascularisation is indicated in cases of persistent ischaemia. This case demonstrates percutaneous therapies to bridge towards and help with subsequent surgical revascularisation.
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Transthoracic echocardiography (TTE) is widely utilised within many aspects of clinical practice, as such the demand placed on echocardiography services is ever increasing. In an attempt to provide incremental value for patients and standardise patient care, the British Society of Echocardiography in collaboration with the British Heart Valve Society have devised updated guidance for the indications and triaging of adult TTE requests for TTE services to implement into clinical practice.