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Patients with severe heart disease may have coexisting liver disease from various causes. The incidence of combined heart-liver transplant (CHLT) is increasing as more patients with congenital heart disease survive to adulthood and develop advanced heart failure with associated liver disease from chronic right-sided heart or Fontan failure. However, the criteria for CHLT have not been established. To address this unmet need, a virtual consensus conference was organized on June 10, 2022, endorsed by the American Society of Transplantation. The conference represented a collaborative effort by experts in cardiothoracic and liver transplantation from across the United States to assess interdisciplinary criteria for liver transplantation in the CHLT candidate, surgical considerations of CHLT, current allocation system that generally results in the liver following the heart for CHLT, and optimal post-CHLT management. The conference served as a forum to unify criteria between the different specialties and to forge a pathway for patients who may need dual organ transplantation. Due to the continuing shortage of available donor organs, ethical issues related to multiorgan transplantation were also debated. The findings and consensus statements are presented.
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Transplante de Coração , Hepatopatias , Transplante de Fígado , Humanos , CoraçãoRESUMO
BACKGROUND: We investigated variables impacting waitlist times and negative waitlist outcomes in adults with congenital heart disease (ACHD) who were waiting for orthotopic heart transplant (OHT) after the 2018 allocation change. METHODS: Adult candidates for OHT who were listed between 10/18/2018 and 12/31/2022 in the United Network for Organ Sharing database were categorized as ACHD vs non-ACHD. Waitlist time and time to upgrade for those upgraded into status 1-3 were compared by using rank-sum tests. Death/delisting for deterioration was assessed by using Fine-Gray subdistribution hazard ratios (SHRs). RESULTS: Of 15,424 OHT candidates, 589 (3.8%) were ACHD. ACHD vs non-ACHD candidates had less urgent status at initial listing (4.2% vs 4.7% listed at status 1; 17.2% vs 23.7% listed at status 2; P < 0.001), but not final listing (5.9% vs 7.6% final status 1; 35.6% vs 36.8% final status 2; P < 0.001). ACHD vs non-ACHD candidates upgraded into status 1 (65.0 vs 30.0 days; Pâ¯=â¯0.09) and status 2 (113.0 vs 64.0 days; Pâ¯=â¯0.003) spent longer times on the waitlist. ACHD vs non-ACHD candidates spent longer times waiting for an upgrade into status 1 (51.4 vs 17.6 days; Pâ¯=â¯0.027) and status 2 (76.7 vs 34.7 days; Pâ¯=â¯0.003). Once upgraded, there was no difference between groups in waitlist time to status 1 (9.7 vs 5.5 daysâ¯=â¯0.66). ACHD vs non-ACHD candidates with a final status of 1 (20.0% vs 8.6%; SHR 2.47 [95%CIâ¯=â¯1.19-5.16]; Pâ¯=â¯0.02) and 2 (8.9% vs 2.3%; SHR 3.59 [95%CIâ¯=â¯2.18-5.91]; P < 0.001) experienced higher rates of death and deterioration. CONCLUSIONS: ACHD candidates have longer waitlist times, have lower priority status at initial listing, wait longer for upgrades, and have higher mortality rates at the same final status as non-ACHD candidates, suggesting that they are being upgraded too late.
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INTRODUCTION: Higher donor sequence numbers (DSNs) might spark provider concern about poor donor quality. We evaluated characteristics of high-DSN offers used for transplant and compared outcomes of high- and low-DSN transplants. MATERIALS AND METHODS: Adult isolated heart transplants between January 1, 2015, and December 31, 2022, were identified from the organ procurement and transplantation network database and stratified into high (≥42) and low (<42) DSN. Postoperative outcomes, including predischarge complications, hospital length of stay, and survival at 1 and 3 y, were evaluated using multivariable regressions. RESULTS: A total of 21,217 recipients met the inclusion criteria, with 2131 (10.0%) classified as high-DSN. Donor factors associated with greater odds of high-DSN at acceptance included older age, higher creatinine, diabetes, hypertension, and lower left ventricular ejection fraction. Recipients accepting high-DSN offers were older and more likely to be female, of blood type O, and have lower status at transplant. High- and low-DSN transplants had similar likelihood of stroke (3.2% versus 3.5%; P = 0.97), dialysis (12.3% versus 13.5%; P = 0.12), pacemaker implant (2.3% versus 2.1%; P = 0.64), had similar lengths of stay (16 [12-24] versus 16 [12-25] days, P = 0.38), and survival at 1 (91.6% versus 91.6%; aHR 0.85 [0.72-1.02], P = 0.08) and 3 y (84.2% versus 85.1%; aHR 0.91 [0.79-1.05], P = 0.21) post-transplant. CONCLUSIONS: High-DSN (≥42) was not an independent risk factor for post-transplant mortality and should not be the sole deterrent to acceptance. Accepting high-DSN organs may increase access to transplantation for lower-status candidates.
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Transplante de Coração , Doadores de Tecidos , Transplante de Coração/efeitos adversos , Transplante de Coração/estatística & dados numéricos , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Doadores de Tecidos/estatística & dados numéricos , Idoso , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Resultado do Tratamento , Tempo de Internação/estatística & dados numéricosRESUMO
INTRODUCTION: Transplants with hearts and lungs from donors with hepatitis C virus (HCV D+) have been proven safe and effective since development of direct-acting antivirals, yet the presence of HCV + persists as a reason to decline organs. METHODS: We identified adult candidates listed January 1, 2015-March 8, 2023 for heart or lung transplant using the Scientific Registry of Transplant Recipients. We identified individual-level and center-level characteristics associated with listing to consider HCV D+ offers using multilevel logistic regression in a multivariable framework. RESULTS: Over the study period, the annual percentage of candidates willing to consider HCV D+ offers increased for both heart (9.5%-74.3%) and lung (7.8%-59.5%), as did the percentage of centers listing candidates for HCV D+ heart (52.9%-91.1%) and lung (32.8%-82.8%) offers. Candidates at centers with more experience with HCV D+ transplants were more likely to consider HCV D+ organ offers. After adjustment, listing center explained 70% and 78% of the residual variance in willingness to consider HCV D+ hearts and lungs, respectively. CONCLUSIONS: Although listing for consideration of HCV D+ offers has increased, it varies by transplant center. Center-level barriers to consideration of HCV D+ organs reduce recipients' transplant access.
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BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has gained traction as a bridge to heart transplantation (HT) but remains associated with increased waitlist mortality. This study explores whether this risk is modified by underlying heart failure (HF) etiology. METHODS: Using the Organ Procurement and Transplantation Network registry, we conducted a retrospective review of first-time adult HT candidates from 2018 through 2022. Patients were categorized as "ECMO", if ECMO was utilized during the waitlisting period, or "No ECMO" otherwise. Patients were then stratified according to the following HF etiology: ischemic cardiomyopathy (CMP), dilated nonischemic CMP, restrictive CMP, hypertrophic CMP, and congenital heart disease (CHD). After baseline comparisons, waitlist mortality was characterized for ECMO and HF etiology using the Fine-Gray regression. RESULTS: A total of 16 143 patients were identified of whom 7.0% (n = 1063) were bridged with ECMO. Compared to No ECMO patients, ECMO patients had shorter waitlist durations (46.3 vs. 185.0 days, p < 0.01) and were more likely to undergo transplantation (75.3% vs. 70.3%, p < 0.01). Outcomes analysis revealed that ECMO was associated with increased mortality risk (subdistribution hazard ratio [SHR]: 3.42, p < 0.01), a risk that persisted in all subgroups and was notably high in CHD (SHR: 4.83, p < 0.01) and hypertrophic CMP (SHR: 9.78, p < 0.01). HF etiology comparison within ECMO patients revealed increased mortality risk with CHD (SHR: 3.22, p < 0.01). Within No ECMO patients, hypertrophic CMP patients had lower mortality risk (SHR: 0.64, p = 0.03). CONCLUSIONS: The increased waitlist mortality risk with ECMO persisted after stratification by HF etiology. These findings can help decision-making surrounding candidacy for cannulation and prognostic evaluation.
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Oxigenação por Membrana Extracorpórea , Insuficiência Cardíaca , Transplante de Coração , Listas de Espera , Humanos , Oxigenação por Membrana Extracorpórea/mortalidade , Transplante de Coração/mortalidade , Masculino , Listas de Espera/mortalidade , Feminino , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/cirurgia , Estudos Retrospectivos , Pessoa de Meia-Idade , Prognóstico , Seguimentos , Taxa de Sobrevida , Fatores de Risco , Sistema de Registros , Adulto , Obtenção de Tecidos e ÓrgãosRESUMO
OBJECTIVE: While stroke is a well-recognized complication of isolated heart transplantation, stroke in patients undergoing simultaneous heart-liver (HLT) and heart-kidney transplantation (HKT) has not been explored. This study assessed postoperative stroke incidence, risk factors, and outcomes in HLT and HKT compared with isolated heart transplant. METHODS: The United Network for Organ Sharing database was queried for adult patients undergoing HLT, HKT, and isolated heart transplants between 1994 and 2022. Patients were stratified by presence of in-hospital stroke after transplant. Post-transplant survival at 1-year was assessed using Kaplan-Meier analysis and log-rank tests. Separate multivariable logistic regression models were constructed to identify risk factors for stroke after HKT and HLT. RESULTS: Of 2326 HKT recipients, 85 experienced stroke, and of 442 HLT recipients, 19 experienced stroke. Stroke was more common after HKT and HLT than after an isolated heart transplant (3.7% vs. 4.3% vs. 2.9%, p = 0.01). One-year post-transplant survival was lower in those with stroke among both HKT recipients (64.5% vs. 88.7%, p(log-rank) < 0.001) and HLT recipients (43.8% vs. 87.4%, p(log-rank) < 0.001. Pre-transplant pVAD, prior stroke, postoperative dialysis, diabetes, prior cardiac surgery, and heart cold ischemic time were independent risk factors for stroke after HKT, after adjusting for age, sex, and need for blood transfusion on the waitlist. For HLT, postoperative dialysis was a significant risk factor. CONCLUSIONS: Stroke is more common after HKT and HLT than after isolated heart transplant, and results in poor survival. Independent risk factors for stroke include pre-transplant percutaneous VAD (HKT) and postoperative dialysis (HKT and HLT).
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Transplante de Coração , Transplante de Rim , Transplante de Fígado , Complicações Pós-Operatórias , Acidente Vascular Cerebral , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Fatores de Risco , Incidência , Transplante de Coração/efeitos adversos , Transplante de Fígado/efeitos adversos , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Seguimentos , Transplante de Rim/efeitos adversos , Prognóstico , Taxa de Sobrevida , Adulto , Estudos Retrospectivos , Sobrevivência de EnxertoRESUMO
Stroke is a well-characterized complication of isolated heart and lung transplantation, but has not been described in combined heart-lung transplantation (HLTx). We retrospectively reviewed national U.S. data to describe the incidence, risk factors, and impact of postoperative stroke in HLTx recipients. Of 871 heart-lung recipients between 1994-2022, 35 (4.0%) experienced stroke, and the incidence increased over time, trending toward significance (p-trend = .07). After adjustment, extracorporeal membrane oxygenation (ECMO) (Adjusted odds ratio [aOR] = 2.63, 95%CI = [1.13-6.11]) and pre-transplant implantable defibrillator (aOR = 2.86, 95%CI = [1.20-6.81]) were independent risk factors for stroke. Postoperative stroke is common and is increasing in an era where organ allocation is driven by mechanical circulatory support (MCS) bridging.
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Transplante de Coração , Transplante de Coração-Pulmão , Humanos , Transplante de Coração-Pulmão/efeitos adversos , Transplante de Coração/efeitos adversos , Estudos Retrospectivos , Incidência , Resultado do Tratamento , Sistema de Registros , Fatores de RiscoRESUMO
We present the case of a previously healthy 13-year-old boy who was admitted to the emergency department with acute flaccid paralysis. Magnetic resonance imaging revealed radiological evidence of longitudinally extensive transverse myelitis. Additionally, homogeneous T2 signal increase was observed in the pons and medulla oblongata, initially indicating brainstem encephalitis. Subsequent evaluations confirmed a coexistence of diffuse midline glioma (DMG) in the brain stem alongside acute transverse myelitis (ATM). Children with ATM generally have a more favorable prognosis than adults. However, despite the implementation of advanced treatment methods, the patient's quadriplegia did not improve and resulted in spinal cord sequela atrophy. DMG exhibits an aggressive growth pattern and lacks a known curative treatment. This case represents an exceedingly rare synchronous occurrence of aggressive conditions, underscoring the importance of raising awareness among physicians. Furthermore, we aim to discuss the radiologic differential diagnosis, as this is the first documented instance in the literature.
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Encefalite , Glioma , Mielite Transversa , Masculino , Adulto , Criança , Humanos , Adolescente , Mielite Transversa/complicações , Mielite Transversa/diagnóstico por imagem , Tronco Encefálico/diagnóstico por imagem , Tronco Encefálico/patologia , Glioma/complicações , Glioma/diagnóstico por imagem , Glioma/patologia , Imageamento por Ressonância MagnéticaRESUMO
The spices and aromatic herbs were used not only in cooking to add flavour and smell to dishes but also for medicinal use. Nigella sativa, also called black cumin, is one of the species that contains an important bioactive component, thymoquinone (TQ), which has antioxidant, anti-inflammatory, antimicrobial, and antidiabetic effects. Curcuma longa, which also includes curcumin, has numerous anti-cancer properties. However, the bioavailability of curcumin is lower than that of its analogs. An analog of curcumin (EF-24), which has better bioavailability than curcumin, is capable of exerting a high anti-cancer effect. In our study, we determined the effects of PON1 enzyme activity on the proliferation and aggressiveness of glioblastoma cancer treated with TQ and EF-24 from lysates of the glioblastoma cell line U87MG. The results were determined as increased PON1 activity after treatment with TQ and EF-24 in the U87MG cell line (p < 0.0001).
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Arildialquilfosfatase , Benzoquinonas , Proliferação de Células , Curcumina , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Glioblastoma , Humanos , Arildialquilfosfatase/metabolismo , Arildialquilfosfatase/antagonistas & inibidores , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Benzoquinonas/farmacologia , Benzoquinonas/química , Curcumina/farmacologia , Curcumina/química , Curcumina/síntese química , Proliferação de Células/efeitos dos fármacos , Estrutura Molecular , Relação Estrutura-Atividade , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Células Tumorais CultivadasRESUMO
INTRODUCTION: We investigated how the 2018 Organ Procurement and Transplantation Network heart allocation policy change was associated with changes in characteristics and outcomes of candidates receiving multiple temporary mechanical circulatory support (mtMCS) devices. MATERIALS AND METHODS: We included adult heart transplant candidates listed October 2014-January 2018 and October 2018-January 2022 in the United Network of Organ Sharing dataset. Prepolicy and postpolicy mtMCS recipients were compared at listing, transplant, 90-days, and 1-year post-transplant. Time between first and second devices and time between first device and transplant were modeled via multivariable linear regression. Transplantation likelihood was modeled using competing risks analysis. RESULTS: Postpolicy, a higher proportion of transplant candidates received mtMCS (4% versus 1%, P < 0.001), and received their second device an adjusted 49 d sooner versus prepolicy (P = 0.001). Time to transplant was also an adjusted 35 d shorter postpolicy, with an 80% increased transplantation likelihood versus prepolicy (95% confidence interval: 1.6-1.9, P < 0.001). Postpolicy patients experienced reduced waitlist mortality (8% versus 14%, P = 0.04) with marked improvements in 90-day (93% versus 85%, P < 0.001) and 1-year (88% versus 70%, P = 0.01) post-transplant survival. CONCLUSIONS: Postpolicy mtMCS recipients are more likely to progress to transplantation sooner on the waitlist and their shorter waitlist course together with earlier change to a secondary device was associated with improved post-transplant survival versus prepolicy.
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Insuficiência Cardíaca , Transplante de Coração , Coração Auxiliar , Obtenção de Tecidos e Órgãos , Adulto , Humanos , Medição de Risco , Probabilidade , Fatores de Tempo , Listas de Espera , Estudos RetrospectivosRESUMO
PURPOSE: Autosomal dominant polycystic kidney disease (ADPKD) is a renal disease with genetic transmisson. Mutations in the PKD1 and PKD2 genes, which encode integral membrane proteins of the cilia of primary renal tubule epithelial cells, are seen in ADPKD. The aim of this study was to evaluate the sinonasal epithelium, which is epithelium with cilia, by measuring the nasal mucociliary clearance time, and to investigate the effect of ADPKD on nasal mucociliary clearance. METHODS: The study included 34 patients, selected from patients followed up in the Nephrology Clinic, and 34 age and gender-matched control group subjects. The nasal mucociliary clearance time (NMCT) was measured with the saccharin test. RESULTS: The mean age of the study subjects was 47.15 ± 14.16 years in the patient group and 47.65 ± 13.85 years in the control group. The eGFR rate was determined as mean 72.06 ± 34.26 mL/min in the patient group and 99.79 ± 17.22 mL/min in the control group (p < 0.001). The NMCT was determined to be statistically significantly longer in the patient group (903.6 ± 487.8 s) than in the control group (580 ± 259 s) (p = 0.006). CONCLUSIONS: The study results showed that the NMCT was statistically significantly longer in patients with ADPKD compared to the control group, but in the linear regression analysis results, no correlation was determined between eGFR and NMCT.
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Depuração Mucociliar , Nariz , Rim Policístico Autossômico Dominante , Adulto , Humanos , Pessoa de Meia-Idade , Depuração Mucociliar/fisiologia , Mutação , Rim Policístico Autossômico Dominante/complicações , Rim Policístico Autossômico Dominante/genética , Rim Policístico Autossômico Dominante/fisiopatologia , Sacarina , Canais de Cátion TRPP/genética , Proteínas de Membrana/genética , Seios Paranasais/fisiopatologia , Mucosa Nasal/fisiopatologia , Nariz/fisiopatologiaRESUMO
With the demand for heart transplantation continuing to outpace the available donor organs, previously underutilized donors are now being reconsidered. We sought to describe the emerging techniques and outcomes of expanded criteria heart transplantation. A comprehensive review of the recent literature concerning expanded donor selection in heart transplantation was performed using the PubMed MEDLINE database. To characterize trends in transplant practice, the United Network for Organ Sharing (UNOS/OPTN) registry was queried for all adult isolated heart transplants since 2010, and data regarding transplant parameters was collected. Donation after cardiac death (DCD), DCD with normothermic regional perfusion, increased ischemic time, hepatitis C positive donor organs, HIV-positive donor organs, and extended criteria donors were identified as promising avenues currently being explored to expand the number of donor organs. The utilization of various expanded criteria for heart transplantation was summarized since 2010 and showed an increasing use of these donor organs, contributing to the overall increasing frequency of heart transplantation. Utilization of expanded criteria for donor selection in heart transplantation has the potential to increase the supply of donor organs with comparable outcomes in selected recipients.
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Infecções por HIV , Transplante de Coração , Hepatite C , Obtenção de Tecidos e Órgãos , Adulto , Humanos , Doadores de Tecidos , Isquemia , Sobrevivência de EnxertoRESUMO
BACKGROUND: Costs and readmissions associated with type A aortic dissection repairs are not well understood. We investigated statewide readmissions, costs, and outcomes associated with the surgical management of type A aortic dissection repairs at low- and high-volume centers. METHODS: We identified all adult type A aortic dissection patients who underwent operative repair in the Maryland Health Services Cost Review Commission's database (2012-2020). Hospitals were stratified into high- (top quartile of total repairs) or low-volume centers. RESULTS: Of the 249 patients included, 193 (77.5%) were treated at a high-volume center. Patients treated at high- and low-volume centers had no differences in age, sex, race, primary payer, or severity (all p > 0.5). High- compared to low-volume centers had a greater proportion of patients transferred in (71.5% vs. 17.9%, p < 0.001). High-volume centers also had longer lengths of stay (12 vs. 8 days, p < 0.001), similar inpatient mortality (13.0% vs. 16.1%, p = 0.6), and similar proportion of patients readmitted (54.9% vs. 51.8%, p = 0.7). High-volume centers had greater index admission costs ($114,859 vs. $72,090, p < 0.001) and similar readmission costs ($48,367 vs. $42,204, p = 0.5). At high-volume centers, transferred patients compared to direct admissions had greater severity of illness (p = 0.05), similar mortality (p = 0.53), and greater lengths of stay (p = 0.05). CONCLUSIONS: High-volume centers had a greater number of patients transferred from other institutions compared to low-volume centers. High-volume centers were associated with increased index admission resource utilization, with transfer patients having higher illness severity and greater resource utilization, yet similar mortality, compared to direct admission patients.
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Dissecção Aórtica , Readmissão do Paciente , Adulto , Humanos , Hospitalização , Dissecção Aórtica/diagnóstico , Dissecção Aórtica/cirurgia , Admissão do Paciente , Hospitais , Estudos RetrospectivosRESUMO
BACKGROUND: Available literature indicates the possible detrimental effect of sex mismatching on mortality in patients undergoing heart transplantation. Our objective was to examine the role of sex and heart mass (predicted heart mass [PHM]) mismatch on mortality and graft rejection in patients undergoing heart transplantation in the US. METHODS: Data on adult patients who underwent heart transplantation between January 2015 and October 2021 were queried from the United Network of Organ Sharing (UNOS) registry. The main outcomes were all-cause mortality, 1-year all-cause mortality and treated acute rejection. RESULTS: A total of 19 805 adult patients underwent heart transplant during the study period. 92.2% of the patients in the female graft to male group had a PHM mismatch <25%, while only 38.5% had such a mismatch in the male graft to female group. In male to male and female to female groups, 79% and 76% of the patients had a PHM mismatch <25% (p = .122). Proportion of PHM mismatch was similar throughout the study period. Unadjusted analysis showed that male recipients of female grafts had increased risk for all-cause mortality (hazard ratio [HR]: 1.13; 95% confidence intervals [CI]: 1.02, 1.27; p = .026) and 1-year mortality (HR: 1.26; 95% CI: 1.09, 1.45; p = .002) compared to male recipients of male grafts. Graft failure incidence was also higher (HR: 1.12; 95% CI: 1.01, 1.25; p = .041). However, all these associations were non- significant after risk factor adjustment. CONCLUSIONS: Sex mismatching is associated with post-transplant mortality with transplantation of female donor grafts to male recipients demonstrating worse outcomes, although this association disappears after risk factor adjustment. Further research is required to elucidate the need for potential changes in clinical practice.
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Transplante de Coração , Transplante de Rim , Adulto , Humanos , Masculino , Feminino , Estados Unidos/epidemiologia , Transplante de Coração/efeitos adversos , Doadores de Tecidos , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/etiologia , Sistema de Registros , Estudos Retrospectivos , Sobrevivência de EnxertoRESUMO
Developing new anticancer agents are crucial for cancer treatment. Antiproliferative activity of L1H as a bis-structured Schiff base was subjected to preliminary research in eight different kinds of cell lines by the cell viability method using different concentrations to determine their inhibitory concentration. L1H demonstrated the highest cytotoxicity in human breast cancer cell line MCF-7. In this perspective, the MCF-7 cell line was cultured for the examination of different molecular techniques, including MTT, apoptosis analysis by enzyme-linked immunosorbent assay (ELISA), and comet assay. Moreover, the DNA ladder, acridine orange/ethidium bromide as another apoptotic cell analysis, markers of oxidative stress, and total antioxidant status, total thiol, and GSH as nonenzymatic antioxidants assay were conducted. The above techniques have proven that L1H is a growth inhibitor effect when compared to cisplatin as a positive control in human breast cancer cells, especially those affected by L1H. The findings clearly show that L1H evaluated in MCF-7 cell lines causes rising or induced apoptosis, DNA damage, diminished antioxidant status against the increase of oxidized protein, and prevents cell proliferation. Manifold evidence supported our hypothesis that L1H has a potential therapeutically improved effect against the MCF-7 cell line, and then without a doubt is a suitable candidate drug for investigating cancers next.
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Antineoplásicos , Neoplasias da Mama , Laranja de Acridina , Antineoplásicos/farmacologia , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Apoptose , Neoplasias da Mama/tratamento farmacológico , Proliferação de Células , Cisplatino/farmacologia , DNA , Dano ao DNA , Etídio , Feminino , Inibidores do Crescimento/farmacologia , Humanos , Células MCF-7 , Bases de Schiff/farmacologia , Compostos de SulfidrilaRESUMO
Multisystemic inflammatory syndrome (MIS-C) diagnosis remains difficult because the clinical features overlap with Kawasaki disease (KD). The study aims to highlight the clinical and laboratory features and outcomes of patients with MISC whose clinical manifestations overlap with or without KD. This study is a retrospective analysis of a case series designed for patients aged 1 month to 18 years in 28 hospitals between November 1, 2020, and June 9, 2021. Patient demographics, complaints, laboratory results, echocardiographic results, system involvement, and outcomes were recorded. A total of 614 patients were enrolled; the median age was 7.4 years (interquartile range (IQR) 3.9-12 years). A total of 277 (45.1%) patients with MIS-C had manifestations that overlapped with KD, including 92 (33.3%) patients with complete KD and 185 (66.7%) with incomplete KD. Lymphocyte and platelet counts were significantly lower in patients with MISC, overlapped with KD (lymphocyte count 1080 vs. 1280 cells × µL, p = 0.028; platelet count 166 vs. 216 cells × 103/µL, p < 0.001). The median serum procalcitonin levels were statistically higher in patients overlapped with KD (3.18 vs. 1.68 µg/L, p = 0.001). Coronary artery dilatation was statistically significant in patients with overlap with KD (13.4% vs. 6.8%, p = 0.007), while myocarditis was significantly more common in patients without overlap with KD features (2.6% vs 7.4%, p = 0.009). The association between clinical and laboratory findings and overlap with KD was investigated. Age > 12 years reduced the risk of overlap with KD by 66% (p < 0.001, 95% CI 0.217-0.550), lethargy increased the risk of overlap with KD by 2.6-fold (p = 0.011, 95% CI 1.244-5.439), and each unit more albumin (g/dl) reduced the risk of overlap with KD by 60% (p < 0.001, 95% CI 0.298-0.559). CONCLUSION: Almost half of the patients with MISC had clinical features that overlapped with KD; in particular, incomplete KD was present. The median age was lower in patients with KD-like features. Lymphocyte and platelet counts were lower, and ferritin and procalcitonin levels were significantly higher in patients with overlap with KD. WHAT IS KNOWN: ⢠In some cases of MIS-C, the clinical symptoms overlap with Kawasaki disease. ⢠Compared to Kawasaki disease, lymphopenia was an independent predictor of MIS-C. WHAT IS NEW: ⢠Half of the patients had clinical features that overlapped with Kawasaki disease. ⢠In patients whose clinical features overlapped with KD, procalcitonin levels were almost 15 times higher than normal. ⢠Lethargy increased the risk of overlap with KD by 2.6-fold in MIS-C patients. ⢠Transient bradycardia was noted in approximately 10% of our patients after initiation of treatment.
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COVID-19 , Síndrome de Linfonodos Mucocutâneos , COVID-19/complicações , COVID-19/diagnóstico , Criança , Pré-Escolar , Humanos , Letargia , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Pró-Calcitonina , Estudos Retrospectivos , SARS-CoV-2 , Síndrome de Resposta Inflamatória SistêmicaRESUMO
AIM: SARS-CoV-2 infection in children is generally asymptomatic or mild; however, it can lead to a life-threatening clinical condition, multisystem inflammatory syndrome in children (MIS-C), days or weeks after the infection. Increased intestinal permeability isa possible triggering factor at the onset of the hyperinflammation associated with MIS-C. Zonulin and claudin-5 are involved in intestinal permeability. In this study, we aimed to investigate serum zonulin and claudin-5 levels in SARS-CoV-2 infection and MIS-C disease. METHODS: The study group consisted of children diagnosed with MIS-C or SARS-CoV-2 infection who presented to a university hospital paediatric emergency or infectious diseases departments. The control group included well patients seen at the General Pediatrics units for routine follow-up. Serum zonulin and claudin-5 levels were measured at the time of diagnosis. RESULTS: Fifteen patients were included in the MIS-C group, 19 in the SARS-CoV-2 infection group and 21 in the control group. The mean zonulin level in the MIS-C group was significantly higher than in the control group (P < 0.001). Mean Claudin-5 levels were Psignificantly lower in the SARS-CoV-2 infection group than in the control group (P < 0.001). CONCLUSION: These results indicate that increased intestinal permeability may be involved in the pathogenesis of SARS-CoV-2 infection and MIS-C disease. Larger clinical trials are needed to clarify the role of serum zonulin and claudin-5 on intestinal permeability in MIS-C and SARS-CoV-2 infection in children.
Assuntos
COVID-19 , Claudina-5/metabolismo , Haptoglobinas/metabolismo , COVID-19/complicações , Criança , Claudina-5/sangue , Haptoglobinas/análise , Humanos , Precursores de Proteínas , SARS-CoV-2 , Síndrome de Resposta Inflamatória SistêmicaRESUMO
AIM: Multisystem inflammatory syndrome in children (MIS-C) may cause shock and even death in children. The aim of this study is to describe the clinical features, laboratory characteristics and outcome of children diagnosed with MIS-C in 25 different hospitals in Turkey. METHODS: The retrospective study was conducted between 8 April and 28 October 2020 in 25 different hospitals from 17 cities. Data were collected from patients' medical records using a standardised form. Clinical and laboratory characteristics and outcomes according to different age groups, gender and body mass index percentiles were compared using multivariate logistic regression analysis. RESULTS: The study comprised 101 patients, median age 7 years (interquartile range (IQR) 4.6-9.3); 51 (50.5%) were boys. Reverse-transcriptase polymerase chain reaction (PCR) assay was positive in 21/100 (21%) patients; 62/83 (74.6%) patients had positive serology for SARS-CoV-2. The predominant complaints were fever (100%), fatigue (n = 90, 89.1%), and gastrointestinal symptoms (n = 81, 80.2%). Serum C-reactive protein (in 101 patients, median 165 mg/L; range 112-228), erythrocyte sedimentation rate (73/84, median 53 mm/s; IQR 30-84) and procalcitonin levels (86/89, median 5 µg/L; IQR 0.58-20.2) were elevated. Thirty-eight patients (37.6%) required admission to intensive care. Kawasaki disease (KD) was diagnosed in 70 (69.3%) patients, 40 of whom had classical KD. Most patients were treated with intravenous immunoglobulin (n = 92, 91%) and glucocorticoids (n = 59, 58.4%). Seven patients (6.9%) died. CONCLUSION: The clinical spectrum of MIS-C is broad, but clinicians should consider MIS-C in the differential diagnosis when persistent fever, fatigue and gastrointestinal symptoms are prominent. Most patients diagnosed with MIS-C were previously healthy. Immunomodulatory treatment and supportive intensive care are important in the management of cases with MIS-C. Glucocorticoids and intravenous immunoglobulins are the most common immunomodulatory treatment options for MIS-C. Prompt diagnosis and prompt treatment are essential for optimal management.
Assuntos
COVID-19 , Síndrome de Linfonodos Mucocutâneos , COVID-19/complicações , Criança , Fadiga , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Estudos Retrospectivos , SARS-CoV-2 , Síndrome de Resposta Inflamatória Sistêmica , Turquia/epidemiologiaRESUMO
OBJECTIVES: Risk assessment models for cardiac surgery do not account for the degrees of liver dysfunction. Ultrasound shear-wave elastography measures liver stiffness (LSM), a quantitative measurement related to fibrosis, congestion, and inflammation. The authors hypothesized that preoperative liver stiffness would be associated with hospital length of stay after cardiac surgery. DESIGN: Prospective observational study. SETTING: University hospital, single center. PARTICIPANTS: One hundred five adult patients undergoing nonemergent cardiac surgery. INTERVENTIONS: Preoperative liver stiffness measured by ultrasound elastography. MEASUREMENTS AND MAIN RESULTS: The associations were analyzed using linear mixed models, with adjustments for preoperative variables, duration of cardiopulmonary bypass, and type of surgery. Median liver stiffness was 6.4 kPa (range, 4.1-18.6 kPa). The median length of hospital stay was 6 days (range, 3-18 d). Each unit increase in liver stiffness, treated as a continuous variable, was associated with an increase of 0.32 ± 0.10 days in the hospital (p = 0.002). When treated as a categorical variable (<6 kPa, 6-9.4 kPa, and ≥9.5 kPa), LSM ≥9.5 kPa v LSM <6 kPa was associated strongly with an increase in hospital length of stay of 3.25 ± 0.87 days (p = 0.0003). CONCLUSIONS: A preoperative LSM ≥9.5 kPa was associated with a significantly longer postoperative hospital length of stay. This association appeared independent of preoperative comorbidities commonly associated with coronary disease. Preoperative liver stiffness is a novel risk metric that is associated with the postoperative hospital length of stay after cardiac surgery.
Assuntos
Procedimentos Cirúrgicos Cardíacos , Cirrose Hepática , Adulto , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Hospitais , Humanos , Tempo de Internação , Fígado , Cirrose Hepática/complicações , Cirrose Hepática/patologiaRESUMO
In this work, novel vic-dioxime ligand (LH2 ) containing bound to the N4 -oxime core moiety and its complexes with Cu(II), Ni(II), Ti(IV), VO(IV), and Zn(II) salts have been studied. The structure of the ligand and its complexes were successfully synthesized and characterized using NMR (1 H and 13 C), LC/MS/MS spectrometer, FT-IR and UV/VIS spectroscopy, melting point, and magnetic susceptibility measurements. Vic-dioxime ligand (LH2 ) (1) and its metal complexes ([Cu(LH)2 ] (2), [Ni(LH)2 ] (3), [Ti(LH)2 ]Cl2 (4), [VO(LH)2 ] (5), and [Zn(LH)2 ] (6), respectively) were tested for them in-vitro antibacterial and antioxidant activities. According to the metal chelating results of the study, it was determined that compounds (1), (2), (3), and (6) showed very good activity, and especially compound (2), had a stronger metal chelating capacity due to ligand dissociation from the synthesized metal complexes, which then would chelate Fe(II) in the experimental setting. When microorganisms were evaluated in terms of the % viability effect, it was observed that all compounds had activity against C.â Albicans and S.â Cerevisiae at rates similar to antibiotics.