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OBJECTIVES: Most post-cardiotomy (PC) extracorporeal membrane oxygenation (ECMO) runs last less than 7 days. Studies on the outcomes of longer runs have provided conflicting results. This study investigates patient characteristics and short- and long-term outcomes in relation to PC ECMO duration, with a focus on prolonged (> 7 d) ECMO. DESIGN: Retrospective observational cohort study. SETTING: Thirty-four centers from 16 countries between January 2000 and December 2020. PATIENTS: Adults requiring post PC ECMO between 2000 and 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Characteristics, in-hospital, and post-discharge outcomes were compared among patients categorized by ECMO duration. Survivors and nonsurvivors were compared in the subgroup of patients with ECMO duration greater than 7 days. The primary outcome was in-hospital mortality. Two thousand twenty-one patients were included who required PC ECMO for 0-3 days (n = 649 [32.1%]), 4-7 days (n = 776 [38.3%]), 8-10 days (n = 263 [13.0%]), and greater than 10 days (n = 333 [16.5%]). There were no major differences in the investigated preoperative and procedural characteristics among ECMO duration groups. However, the longer ECMO duration category was associated with multiple complications including bleeding, acute kidney injury, arrhythmias, and sepsis. Hospital mortality followed a U-shape curve, with lowest mortality in patients with ECMO duration of 4-7 days (n = 394, 50.8%) and highest in patients with greater than 10 days ECMO support (n = 242, 72.7%). There was no significant difference in post-discharge survival between ECMO duration groups. In patients with ECMO duration greater than 7 days, age, comorbidities, valvular diseases, and complex procedures were associated with nonsurvival. CONCLUSIONS: Nearly 30% of PC ECMO patients were supported for greater than 7 days. In-hospital mortality increased after 7 days of support, especially in patients undergoing valvular and complex surgery, or who had complications, although the long-term post-discharge prognosis was comparable to PC ECMO patients with shorter support duration.
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BACKGROUND: Methods for risk stratification of candidates for heart transplantation (HTx) supported by extracorporeal membrane oxygenation (ECMO) are limited. We evaluated the reliability of the APACHE IV score to identify the risk of mortality in this patient subset in a multicenter study. METHODS: Between January 2010 and December 2022, 167 consecutive ECMO patients were bridged to HTx; they were divided into two groups, according to a cutoff value of APACHE IV score, obtained by receiver operating characteristic curve analysis for 90-day mortality. Kaplan-Meier survival curves were plotted, and compared through the log-Rank test. Cox regression model was used to estimate which factors were associated with survival. RESULTS: The 90-day mortality prediction of the APACHE IV score showed an area under the curve of 0.87 (95% CI: 0.80-0.94), with a cutoff value of 49 (specificity 91.7%-sensibility 69.6%). 125 patients (74.8%) showed an APACHE IV score value < 49 (Group A), and 42 (25.2%) ≥ 49 (Group B). 90-day mortality was 11.2% in Group A and 76.2% in Group B (p < 0.01). Survival at 1 and 5 years was 85.5%, 77% versus 23.4%, 23.4% (p < 0.01) in Groups A and B. Mortality correlated at univariable analysis with recipient age, body mass index, mechanical ventilation, APACHE IV score, and platelets number. At multivariable analysis only APACHE IV score (HR: 1.07 [1.05-1.09, 95% CI]) independently affected survival. CONCLUSIONS: The APACHE IV score represents a powerful predictor of survival in patients bridged to HTx on ECMO support, and could guide candidacy of patients on ECMO.
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APACHE , Oxigenação por Membrana Extracorpórea , Transplante de Coração , Humanos , Transplante de Coração/mortalidade , Feminino , Masculino , Prognóstico , Pessoa de Meia-Idade , Seguimentos , Adulto , Taxa de Sobrevida , Estudos Retrospectivos , Fatores de Risco , Curva ROC , Medição de Risco/métodosRESUMO
BACKGROUND: Cerebral perfusion may change depending on arterial cannulation site and may affect the incidence of neurologic adverse events in post-cardiotomy extracorporeal life support (ECLS). The current study compares patients' neurologic outcomes with three commonly used arterial cannulation strategies (aortic vs. subclavian/axillary vs. femoral artery) to evaluate if each ECLS configuration is associated with different rates of neurologic complications. METHODS: This retrospective, multicenter (34 centers), observational study included adults requiring post-cardiotomy ECLS between January 2000 and December 2020 present in the Post-Cardiotomy Extracorporeal Life Support (PELS) Study database. Patients with Aortic, Subclavian/Axillary and Femoral cannulation were compared on the incidence of a composite neurological end-point (ischemic stroke, cerebral hemorrhage, brain edema). Secondary outcomes were overall in-hospital mortality, neurologic complications as cause of in-hospital death, and post-operative minor neurologic complications (seizures). Association between cannulation and neurological outcomes were investigated through linear mixed-effects models. RESULTS: This study included 1897 patients comprising 26.5% Aortic (n = 503), 20.9% Subclavian/Axillary (n = 397) and 52.6% Femoral (n = 997) cannulations. The Subclavian/Axillary group featured a more frequent history of hypertension, smoking, diabetes, previous myocardial infarction, dialysis, peripheral artery disease and previous stroke. Neuro-monitoring was used infrequently in all groups. Major neurologic complications were more frequent in Subclavian/Axillary (Aortic: n = 79, 15.8%; Subclavian/Axillary: n = 78, 19.6%; Femoral: n = 118, 11.9%; p < 0.001) also after mixed-effects model adjustment (OR 1.53 [95% CI 1.02-2.31], p = 0.041). Seizures were more common in Subclavian/Axillary (n = 13, 3.4%) than Aortic (n = 9, 1.8%) and Femoral cannulation (n = 12, 1.3%, p = 0.036). In-hospital mortality was higher after Aortic cannulation (Aortic: n = 344, 68.4%, Subclavian/Axillary: n = 223, 56.2%, Femoral: n = 587, 58.9%, p < 0.001), as shown by Kaplan-Meier curves. Anyhow, neurologic cause of death (Aortic: n = 12, 3.9%, Subclavian/Axillary: n = 14, 6.6%, Femoral: n = 28, 5.0%, p = 0.433) was similar. CONCLUSIONS: In this analysis of the PELS Study, Subclavian/Axillary cannulation was associated with higher rates of major neurologic complications and seizures. In-hospital mortality was higher after Aortic cannulation, despite no significant differences in incidence of neurological cause of death in these patients. These results encourage vigilance for neurologic complications and neuromonitoring use in patients on ECLS, especially with Subclavian/Axillary cannulation.
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Aorta , Oxigenação por Membrana Extracorpórea , Artéria Femoral , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Oxigenação por Membrana Extracorpórea/métodos , Oxigenação por Membrana Extracorpórea/efeitos adversos , Oxigenação por Membrana Extracorpórea/estatística & dados numéricos , Idoso , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/epidemiologia , Adulto , Artéria Subclávia , Cateterismo/métodos , Cateterismo/efeitos adversos , Cateterismo/estatística & dados numéricos , Cateterismo Periférico/métodos , Cateterismo Periférico/efeitos adversos , Cateterismo Periférico/estatística & dados numéricos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Mortalidade Hospitalar/tendênciasRESUMO
OBJECTIVES: Post-cardiotomy extracorporeal life support (ECLS) cannulation might occur in a general post-operative ward due to emergent conditions. Its characteristics have been poorly reported and investigated This study investigates the characteristics and outcomes of adult patients receiving ECLS cannulation in a general post-operative cardiac ward. METHODS: The Post-cardiotomy Extracorporeal Life Support (PELS) is a retrospective (2000-2020), multicenter (34 centers), observational study including adult patients who required ECLS for post-cardiotomy shock. This PELS sub-analysis analyzed patients´ characteristics, in-hospital outcomes, and long-term survival in patients cannulated for veno-arterial ECLS in the general ward, and further compared in-hospital survivors and non-survivors. RESULTS: The PELS study included 2058 patients of whom 39 (1.9%) were cannulated in the general ward. Most patients underwent isolated coronary bypass grafting (CABG, n = 15, 38.5%) or isolated non-CABG operations (n = 20, 51.3%). The main indications to initiate ECLS included cardiac arrest (n = 17, 44.7%) and cardiogenic shock (n = 14, 35.9%). ECLS cannulation occurred after a median time of 4 (2-7) days post-operatively. Most patients' courses were complicated by acute kidney injury (n = 23, 59%), arrhythmias (n = 19, 48.7%), and postoperative bleeding (n = 20, 51.3%). In-hospital mortality was 84.6% (n = 33) with persistent heart failure (n = 11, 28.2%) as the most common cause of death. No peculiar differences were observed between in-hospital survivors and nonsurvivors. CONCLUSIONS: This study demonstrates that ECLS cannulation due to post-cardiotomy emergent adverse events in the general ward is rare, mainly occurring in preoperative low-risk patients and after a postoperative cardiac arrest. High complication rates and low in-hospital survival require further investigations to identify patients at risk for such a complication, optimize resources, enhance intervention, and improve outcomes.
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BACKGROUND: Post-acute myocardial infarction papillary muscle rupture (post-AMI PMR) may present variable clinical scenarios and degree of emergency due to result of cardiogenic shock. Veno-arterial extracorporeal life support (V-A ECLS) has been proposed to improve extremely poor pre- or postoperative conditions. Information in this respect is scarce. METHODS: From the CAUTION (meChanical complicAtion of acUte myocardial infarcTion: an InternatiOnal multiceNter cohort study) database (16 different Centers, data from 2001 to 2018), we extracted adult patients who were surgically treated for post-AMI PMR and underwent pre- or/and postoperative V-A ECLS support. The end-points of this study were in-hospital survival and ECLS complications. RESULTS: From a total of 214 post-AMI PMR patients submitted to surgery, V-A ECLS was instituted in 23 (11%) patients. The median age was 61.7 years (range 46-81 years). Preoperatively, ECLS was commenced in 10 patients (43.5%), whereas intra/postoperative in the remaining 13. The most common V-A ECLS indication was post-cardiotomy shock, followed by preoperative cardiogenic shock and cardiac arrest. The median duration of V-A ECLS was 4 days. V-A ECLS complications occurred in more than half of the patients. Overall, in-hospital mortality was 39.2% (9/23), compared to 22% (42/219) for the non-ECLS group. CONCLUSIONS: In post-AMI PMR patients, V-A ECLS was used in almost 10% of the patients either to promote bridge to surgery or as postoperative support. Further investigations are required to better evaluate a potential for increased use and its effects of V-A ECLS in such a context based on the still high perioperative mortality.
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Cardiomiopatias , Oxigenação por Membrana Extracorpórea , Doenças das Valvas Cardíacas , Infarto do Miocárdio , Adulto , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Oxigenação por Membrana Extracorpórea/métodos , Choque Cardiogênico/etiologia , Choque Cardiogênico/cirurgia , Estudos de Coortes , Músculos Papilares/cirurgia , Infarto do Miocárdio/complicações , Cardiomiopatias/complicações , Doenças das Valvas Cardíacas/complicaçõesRESUMO
The overuse and misuse of antibiotics have led to the emergence and spread of multidrug-resistant (MDR), extensively drug-resistant (XDR), and pan-drug-resistant (PDR) bacteria strains, usually associated with poorer patient outcomes and higher costs. In order to preserve the usefulness of these life-saving drugs, it is crucial to use them appropriately, as also recommended by the WHO. Moreover, innovative, safe, and more effective approaches are being investigated, aiming to revise drug treatments to improve their pharmacokinetics and distribution and to reduce the onset of drug resistance. Globally, to reduce the burden of antimicrobial resistance (AMR), guidelines and indications have been developed over time, aimed at narrowing the use and diminishing the environmental spread of these life-saving molecules by optimizing prescriptions, dosage, and times of use, as well as investing resources into obtaining innovative formulations with better pharmacokinetics, pharmacodynamics, and therapeutic results. This has led to the development of new nano-formulations as drug delivery vehicles, characterized by unique structural properties, biocompatible natures, and targeted activities such as state-of-the-art phospholipid particles generally grouped as liposomes, virosomes, and functionalized exosomes, which represent an attractive and innovative delivery approach. Liposomes and virosomes are chemically synthesized carriers that utilize phospholipids whose nature is predetermined based on their use, with a long track record as drug delivery systems. Exosomes are vesicles naturally released by cells, which utilize the lipids present in their cellular membranes only, and therefore, are highly biocompatible, with investigations as a delivery system having a more recent origin. This review will summarize the state of the art on microvesicle research, liposomes, virosomes, and exosomes, as useful and effective tools to tackle the threat of antibiotic resistance.
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Antibacterianos , Lipossomos , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Fosfolipídeos , Virossomos , Farmacorresistência Bacteriana , BactériasRESUMO
BACKGROUND: We studied the incidence of primary graft dysfunction (PGD), its impact on in-hospital and follow-up outcomes and searched for independent risk factors. METHODS: During an 18-year period, 508 individuals underwent heart transplantation at our institution. Patients were diagnosed with none, mild, moderate or severe PGD according to ISHLT criteria. RESULTS: Thirty-eight patients (7.5%) met the ISHLT criteria for mild PGD, 92 (18.1%) for moderate PGD and 23 (4.5%) for severe PGD. Patients were classified into none/mild PGD (77.4%) and moderate/severe PGD (22.6%) groups. In-hospital mortality was 12.4% (7.8% for none/mild PGD and 28.7% for moderate/severe PGD; p < .001). Survival at 1, 5, and 15 years was 85.5 ± 1.9% versus 67.2 ± 4.5%, 80 ± 2.2% versus 63.5 ± 4.7%, and 60.4 ± 3.6% versus 45.9 ± 8.4%, respectively (p < .001). Excluding the events occurring during the first month of follow-up, survival was comparable between the two groups (93.1 ± 1.4% vs. 94.7 ± 2.6 at 1 year and 65.6 ± 3.8% vs. 70.4 ± 10.4% at 15 years, respectively; p = .88). Upon multivariate logistic regression analysis preoperative mechanical circulatory support (odds ratio [OR] = 5.86) and preoperative intra-aortic balloon pump (IABP) (OR = 9.58) were independently associated with moderate/severe PGD. CONCLUSIONS: Our results confirm that PGD is associated with poor in-hospital outcome. The poor outcome does not extend beyond the first month of follow-up, with comparable survival between patients with none/mild PGD and moderate/severe PGD in the short and long-term. Mechanical circulatory support and preoperative IABP were found to be independent risk factors for moderate/severe PGD.
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Transplante de Coração , Coração Auxiliar , Disfunção Primária do Enxerto , Transplante de Coração/efeitos adversos , Transplante de Coração/métodos , Coração Auxiliar/efeitos adversos , Humanos , Disfunção Primária do Enxerto/epidemiologia , Disfunção Primária do Enxerto/etiologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
The low-density-lipoprotein receptors represent a family of pleiotropic cell surface receptors involved in lipid homeostasis, cell migration, proliferation and differentiation. The family shares common structural features but also has significant differences mainly due to tissue-specific interactors and to peculiar proteolytic processing. Among the receptors in the family, recent studies place low-density lipoprotein receptor-related protein 8 (LRP8) at the center of both neurodegenerative and cancer-related pathways. From one side, its overexpression has been highlighted in many types of cancer including breast, gastric, prostate, lung and melanoma; from the other side, LRP8 has a potential role in neurodegeneration as apolipoprotein E (ApoE) and reelin receptor, which are, respectively, the major risk factor for developing Alzheimer's disease (AD) and the main driver of neuronal migration, and as a γ-secretase substrate, the main enzyme responsible for amyloid formation in AD. The present review analyzes the contributions of LDL receptors, specifically of LRP8, in both cancer and neurodegeneration, pointing out that depending on various interactions and peculiar processing, the receptor can contribute to both proliferative and neurodegenerative processes.
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Doença de Alzheimer , Neoplasias , Doença de Alzheimer/metabolismo , Secretases da Proteína Precursora do Amiloide , Humanos , Lipoproteínas LDL , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade , Masculino , Receptores de LDL/metabolismoRESUMO
Recent studies have highlighted the mechanisms controlling the formation of cerebral cholesterol, which is synthesized in situ primarily by astrocytes, where it is loaded onto apolipoproteins and delivered to neurons and oligodendrocytes through interactions with specific lipoprotein receptors. The "cholesterol shuttle" is influenced by numerous proteins or carbohydrates, which mainly modulate the lipoprotein receptor activity, function and signaling. These molecules, provided with enzymatic/proteolytic activity leading to the formation of peptide fragments of different sizes and specific sequences, could be also responsible for machinery malfunctions, which are associated with neurological, neurodegenerative and neurodevelopmental disorders. In this context, we have pointed out that purines, ancestral molecules acting as signal molecules and neuromodulators at the central nervous system, can influence the homeostatic machinery of the cerebral cholesterol turnover and vice versa. Evidence gathered so far indicates that purine receptors, mainly the subtypes P2Y2, P2X7 and A2A, are involved in the pathogenesis of neurodegenerative diseases, such as Alzheimer's and Niemann-Pick C diseases, by controlling the brain cholesterol homeostasis; in addition, alterations in cholesterol turnover can hinder the purine receptor function. Although the precise mechanisms of these interactions are currently poorly understood, the results here collected on cholesterol-purine reciprocal control could hopefully promote further research.
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Sistema Nervoso Central , Doenças de Niemann-Pick , Sistema Nervoso Central/metabolismo , Colesterol/metabolismo , Humanos , Neurônios/metabolismo , Doenças de Niemann-Pick/metabolismo , Purinas/metabolismo , Receptores Purinérgicos/metabolismoRESUMO
We thank Dr. Sagliocco and Dr. Betelli for their comments [...].
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Parada Cardíaca , Hipotensão , Idoso , Bradicardia/induzido quimicamente , Parada Cardíaca/induzido quimicamente , Humanos , Hipotensão/induzido quimicamente , Sugammadex/efeitos adversosRESUMO
Nowadays, novel oral anticoagulants (NOACs) have shown improved safety profile and efficacy compared to vitamin K antagonists in the prevention of thromboembolic events occurring during different pathological conditions. However, there are concerns and safety issues, mostly related to adverse events following interactions with other drugs, in real-world practice. We report the case of an 83-year-old woman who developed a non-bleeding leg ulcer not caused by trauma or other evident pathological conditions after 10 days of treatment with apixaban 5 mg/q.d. She was switched from apixaban to dabigatran and the leg ulcer rapidly improved and completely cicatrized in 40 days. The resolution of the ulcer and the toleration of dabigatran therapy suggest an apixaban-specific reaction; however, the pathological mechanism of ulcer onset is currently unclear. Careful evaluation of hospital databases of Molise region (Southern Italy) hospitals identified two similar cases between 2019 and 2021. These cases underline the necessity of careful post-marketing surveillance, considering the rapidly increasing number of patients treated with NOACs and patient's risk factors such as old age, high polypharmacy rate, co-morbidities, and peculiar genetic background related to NOACs pharmacokinetic features.
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Fibrilação Atrial , Úlcera da Perna , Administração Oral , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Dabigatrana/efeitos adversos , Feminino , Humanos , Úlcera da Perna/induzido quimicamente , Úlcera da Perna/tratamento farmacológico , Pirazóis , Piridonas , Úlcera/induzido quimicamente , Úlcera/tratamento farmacológicoRESUMO
AIMS: In the last decade, transcatheter aortic valve (TAV) replacement determined a paradigm shift in the treatment of patients with severe symptomatic aortic stenosis. Data on long-term TAV performance are still limited. We sought to evaluate the clinical and haemodynamic outcomes of the CoreValve self-expandable valve up to 8-year follow-up (FU). METHODS AND RESULTS: Nine hundred and ninety inoperable or high-risk patients were treated with the CoreValve TAV in eight Italian Centres from June 2007 to December 2011. The median FU was 4.4 years (interquartile range 1.4-6.7 years). Longest FU reached 11 years. A total of 728 died within 8-year FU (78.3% mortality from Kaplan-Meier curve analysis). A significant functional improvement was observed in the majority of patients and maintained over time, with 79.3% of surviving patients still classified New York Heart Association class ≤ II at 8 years. Echocardiographic data showed that the mean transprosthetic aortic gradient remained substantially unchanged (9 ± 4 mmHg at discharge, 9 ± 5 mmHg at 8 years, P = 0.495). The rate of Grade 0/1 paravalvular leak was consistent during FU with no significant change from post-procedure to FU ≥5 years in paired analysis (P = 0.164). Structural valve deterioration (SVD) and late bioprosthetic valve failure (BVF) were defined according to a modification of the 2017 EAPCI/ESC/EACTS criteria. In cumulative incidence functions at 8 years, moderate and severe SVD were 3.0% [95% confidence interval (CI) 2.1-4.3%] and 1.6% (95% CI 0.6-3.9%), respectively, while late BVF was 2.5% (95% CI 1.2-5%). CONCLUSION: While TAVs are questioned about long-term performance and durability, the results of the present research provide reassuring 8-year evidence on the CoreValve first-generation self-expandable bioprosthesis.
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Estenose da Valva Aórtica , Bioprótese , Próteses Valvulares Cardíacas , Substituição da Valva Aórtica Transcateter , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/cirurgia , Humanos , Desenho de Prótese , Falha de Prótese , Resultado do TratamentoRESUMO
ABSTRACT: Lymphatic leaks are common following common femoral vessel exposure for cardiac surgical procedures. The management of this complication can be difficult and is often uncomfortable for the patient. This case report describes the successful nonoperative treatment of a recurrent lymphatic leak from an inguinal surgical wound via negative-pressure wound therapy. Negative pressure may be considered a minimally invasive, effective, and acceptable way to treat postoperative lymphatic leaks at the groin.
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Virilha/cirurgia , Tratamento de Ferimentos com Pressão Negativa/normas , Humanos , Masculino , Tratamento de Ferimentos com Pressão Negativa/métodos , Tratamento de Ferimentos com Pressão Negativa/estatística & dados numéricos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/fisiopatologia , Adulto JovemRESUMO
Background and Objectives: Sugammadex is a modified γ-cyclodextrin largely used to prevent postoperative residual neuromuscular blockade induced by neuromuscular aminosteroid blocking agents. Although Sugammadex is considered more efficacious and safer than other drugs, such as Neostigmine, significant and serious complications after its administration, such as hypersensitivity, anaphylaxis and, more recently, severe cardiac events, are reported. Case presentation: In this report, we describe the case of an 80-year-old male with no medical history of cardiovascular disease who was scheduled for percutaneous nephrolithotripsy under general anesthesia. The intraoperative course was uneventful; however, the patient developed a rapid and severe hypotension, asystole and cardiac arrest after Sugammadex administration. Spontaneous cardiac activity and hemodynamic stability was restored with pharmacological therapy and chest compression. The patient was stabilized and discharged uneventfully on postoperative day 10. Conclusions: The potential causes of cardiac arrest after Sugammadex administration have been carefully considered, yet all indications point to Sugammadex as the direct causative agent. On the basis of laboratory and clinical tests, we can exclude among the cause of bradycardia, Kounis syndrome, acute myocardial infarction, coronary spasm and other arrhythmias, but not anaphylaxis. Although Sugammadex is considered an increasingly important option in the prevention of postoperative residual neuromuscular blockade, anesthesiologists should consider it a causative agent of cardiac arrest during surgery. This case highlights the necessity of increased pharmacovigilance and further studies to examine Sugammadex safety and mechanism through which it may cause severe bradycardia, hypotension and cardiac arrest.
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Parada Cardíaca , Hipotensão , Cálculos Renais , Litotripsia , Bloqueio Neuromuscular , Idoso , Idoso de 80 Anos ou mais , Bradicardia/induzido quimicamente , Inibidores da Colinesterase , Parada Cardíaca/induzido quimicamente , Humanos , Hipotensão/induzido quimicamente , Masculino , Sugammadex/efeitos adversosRESUMO
INTRODUCTION: Non-invasive prenatal testing (NIPT) using cell-free foetal DNA has been widely accepted in recent years for detecting common foetal chromosome aneuploidies, such as trisomies 13, 18 and 21, and sex chromosome aneuploidies. In this study, the practical clinical performance of our foetal DNA testing was evaluated for analysing all chromosome aberrations among 7113 pregnancies in Italy. METHODS: This study was a retrospective analysis of collected NIPT data from the Ion S5 next-generation sequencing platform obtained from Altamedica Medical Centre in Rome, Italy. RESULTS: In this study, NIPT showed 100% sensitivity and 99.9% specificity for trisomies 13, 18 and 21. Out of the 7113 samples analysed, 74 cases (1%) were positive by NIPT testing; foetal karyotyping and follow-up results validated 2 trisomy 13 cases, 5 trisomy 18 cases, 58 trisomy 21 cases and 10 sex chromosome aneuploidy cases. There were no false-negative results. CONCLUSION: In our hands, NIPT had high sensitivity and specificity for common chromosomal aneuploidies such as trisomies 13, 18 and 21.
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Aneuploidia , Ácidos Nucleicos Livres/análise , Síndrome de Down/diagnóstico , Testes Genéticos/métodos , Diagnóstico Pré-Natal/métodos , Síndrome da Trissomia do Cromossomo 13/diagnóstico , Síndrome da Trissomía do Cromossomo 18/diagnóstico , Adulto , Ácidos Nucleicos Livres/genética , Síndrome de Down/epidemiologia , Síndrome de Down/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Itália/epidemiologia , Programas de Rastreamento , Pessoa de Meia-Idade , Gravidez , Estudos Retrospectivos , Síndrome da Trissomia do Cromossomo 13/epidemiologia , Síndrome da Trissomia do Cromossomo 13/genética , Síndrome da Trissomía do Cromossomo 18/epidemiologia , Síndrome da Trissomía do Cromossomo 18/genética , Adulto JovemRESUMO
PURPOSE: Heritable thoracic aortic disease can result from null variants in MYLK, which encodes myosin light-chain kinase (MLCK). Data on which MYLK missense variants are pathogenic and information to guide aortic disease management are limited. METHODS: Clinical data from 60 cases with MYLK pathogenic variants were analyzed (five null and two missense variants), and the effect of missense variants on kinase activity was assessed. RESULTS: Twenty-three individuals (39%) experienced an aortic event (defined as aneurysm repair or dissection); the majority of these events (87%) were aortic dissections. Aortic diameters were minimally enlarged at the time of dissection in many cases. Time-to-aortic-event curves showed that missense pathogenic variant (PV) carriers have earlier-onset aortic events than null PV carriers. An MYLK missense variant segregated with aortic disease over five generations but decreases MYLK kinase acitivity marginally. Functional Assays fail to identify all pathogenic variants in MYLK. CONCLUSION: These data further define the aortic phenotype associated with MYLK pathogenic variants. Given minimal aortic enlargement before dissection, an alternative approach to guide the timing of aortic repair is proposed based on the probability of a dissection at a given age.
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Doenças da Aorta/genética , Proteínas de Ligação ao Cálcio/genética , Testes Genéticos , Sequenciamento de Nucleotídeos em Larga Escala , Quinase de Cadeia Leve de Miosina/genética , Adulto , Idoso , Dissecção Aórtica , Aorta/patologia , Aorta/cirurgia , Doenças da Aorta/patologia , Doenças da Aorta/cirurgia , Feminino , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , GravidezRESUMO
OBJECTIVE: Left ventricular assist devices (LVADs) are increasingly used for temporary circulatory support until transplant or as destination therapy for patients with end-stage heart failure. Understanding patients' attitudes and resources is crucial to support them. METHODS: Sixty-one LVAD recipients (55 [10] years, 10% women, 15% destination therapy) participating in cardiac rehabilitation (CR) postimplant underwent assessment of coping styles (Coping Orientation for Problem Experiences), quality of life (Medical Outcomes Study Short-Form 36, Minnesota Living with Heart Failure Questionnaire), and mood (Hospital Anxiety and Depression Scale). RESULTS: Cluster analysis identified two homogeneous groups: C1 (n = 18) patients had higher anxiety (9.6 [5.0] versus 4.0 [2.7], p < .001), depression (10 [3.0] versus 4 [2.7], p < .001), and avoidant coping (29 [5.2] versus 21.2 [3.8], p < .001) scores and worse quality of life (Short-Form 36 of the Medical Outcomes Study Physical Component Scale 31 [5.3] versus 35.6 [6.9], p < .001; Mental Component Scale 34.3 [6.8] versus 50.3 [8], p < .001; MLHFQ physical 26 [7.2] versus 13.9 [8.2], p < .001; emotional 17.7 [3.4] versus 3.86 [3.2], p < .001) than C2 participants (n = 43). During 31 (15-54) months, 20 patients (33%) died. By Cox multivariable analysis, after adjustment for age, sex, Interagency Registry for Mechanically Assisted Circulatory Support level at surgery, and meters walked during 6 minutes at CR discharge, C1 was associated with mortality (hazard ratio = 2.858; 95% confidence interval = 1.102-7.408, p = .031; model χ = 7.286, df = 5, p = .20). Survival was 44% in C1 and 77% in C2 (log-rank p = .033). CONCLUSIONS: Among patients discharged from CR after LVAD implant, one third show a profile characterized by worse perceived quality of life, mood disorders, and dysfunctional coping that is associated with long-term mortality, and these factors are potential targets for post-LVAD intensive support.
Assuntos
Adaptação Psicológica/fisiologia , Ansiedade/psicologia , Depressão/psicologia , Insuficiência Cardíaca/psicologia , Insuficiência Cardíaca/terapia , Ventrículos do Coração , Coração Auxiliar , Qualidade de Vida/psicologia , Análise por Conglomerados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: Previous reports have suggested that despite their dramatic presentation, patients with fulminant myocarditis (FM) might have better outcome than those with acute nonfulminant myocarditis (NFM). In this retrospective study, we report outcome and changes in left ventricular ejection fraction (LVEF) in a large cohort of patients with FM compared with patients with NFM. METHODS: The study population consists of 187 consecutive patients admitted between May 2001 and November 2016 with a diagnosis of acute myocarditis (onset of symptoms <1 month) of whom 55 required inotropes and/or mechanical circulatory support (FM) and the remaining 132 were hemodynamically stable (NFM). We also performed a subanalysis in 130 adult patients with acute viral myocarditis and viral prodrome within 2 weeks from the onset, which includes 34 with FM and 96 with NFM. Patients with giant-cell myocarditis, eosinophilic myocarditis, or cardiac sarcoidosis and those <15 years of age were excluded from the subanalysis. RESULTS: In the whole population (n=187), the rate of in-hospital death or heart transplantation was 25.5% versus 0% in FM versus NFM, respectively (P<0.0001). Long-term heart transplantation-free survival at 9 years was lower in FM than NFM (64.5% versus 100%, log-rank P<0.0001). Despite greater improvement in LVEF during hospitalization in FM versus NFM forms (median, 32% [interquartile range, 20%-40%] versus 3% [0%-10%], respectively; P<0.0001), the proportion of patients with LVEF <55% at last follow-up was higher in FM versus NFM (29% versus 9%; relative risk, 3.32; 95% confidence interval, 1.45-7.64, P=0.003). Similar results for survival and changes in LVEF in FM versus NFM were observed in the subgroup (n=130) with viral myocarditis. None of the patients with NFM and LVEF ≥55% at discharge had a significant decrease in LVEF at follow-up. CONCLUSIONS: Patients with FM have an increased mortality and need for heart transplantation compared with those with NFM. From a functional viewpoint, patients with FM have a more severely impaired LVEF at admission that, despite steep improvement during hospitalization, remains lower than that in patients with NFM at long-term follow-up. These findings also hold true when only the viral forms are considered and are different from previous studies showing better prognosis in FM.
Assuntos
Miocardite/diagnóstico , Função Ventricular Esquerda/fisiologia , Doença Aguda , Adolescente , Adulto , Ecocardiografia , Feminino , Seguimentos , Coração/diagnóstico por imagem , Transplante de Coração , Coração Auxiliar , Hemodinâmica , Mortalidade Hospitalar , Humanos , Imunossupressores/uso terapêutico , Estimativa de Kaplan-Meier , Imagem Cinética por Ressonância Magnética , Masculino , Miocardite/mortalidade , Miocardite/terapia , Miocárdio/patologia , Adulto JovemRESUMO
Management of acute decompensated heart failure patients presenting with cardiogenic shock (CS) is not straightforward, as few data are available from clinical trials. Stabilization before left ventricle assist device (LVAD) or heart transplantation (HTx) is strongly advocated, as patients undergoing LVAD implant or HTx in critical status have worse outcomes. This was a multicenter phase II study with a Simon 2-stage design, including 24 consecutive patients treated with low-moderate epinephrine doses, whose refractory CS prompted implantation of intra-aortic balloon pump (IABP) which was subsequently upgraded with peripheral venoarterial extracorporeal membrane oxygenation. At admission, patients had severe left ventricular dysfunction and overt CS, 7 patients could be managed only with inotropic therapy, and 16 patients were transitioned to IABP and 1 to IABP and venoarterial extracorporeal membrane oxygenation; the median duration of epinephrine therapy was 7â¯days (interquartile range 6-15), and the median dose was 0.08 µg/kg/min (interquartile range 0.05-0.1); 21 patients (87.5%) survived at 60â¯days (primary outcome); among them, 13 (61.9%) underwent LVAD implantation, 2 (9.5%) underwent HTx, and 6 (28.6%) improved on medical treatment, indicating that early and intensive treatment of CS in chronic advanced heart failure patients with low-dose epinephrine and timely short-term mechanical circulatory support leads to satisfactory outcomes.
Assuntos
Agonistas Adrenérgicos beta/uso terapêutico , Epinefrina/uso terapêutico , Oxigenação por Membrana Extracorpórea , Insuficiência Cardíaca/complicações , Balão Intra-Aórtico , Choque Cardiogênico/terapia , Vasoconstritores/uso terapêutico , Agonistas Adrenérgicos beta/efeitos adversos , Idoso , Algoritmos , Terapia Combinada , Epinefrina/efeitos adversos , Feminino , Insuficiência Cardíaca/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Choque Cardiogênico/etiologia , Resultado do Tratamento , Vasoconstritores/efeitos adversosRESUMO
There is a paucity of data about mid-term outcome of patients with advanced heart failure (HF) treated with left ventricular assist device (LVAD) in Europe, where donor shortage and their aging limit the availability and the probability of success of heart transplantation (HTx). The aim of this study is to compare Italian single-centre mid-term outcome in prospective patients treated with LVAD vs. HTx. We evaluated 213 consecutive patients with advanced HF who underwent continuous-flow LVAD implant or HTx from 1/2006 to 2/2012, with complete follow-up at 1 year (3/2013). We compared outcome in patients who received a LVAD (n = 49) with those who underwent HTx (n = 164) and in matched groups of 39 LVAD and 39 HTx patients. Patients that were treated with LVAD had a worse risk profile in comparison with HTx patients. Kaplan-Meier survival curves estimated a one-year survival of 75.5 % in LVAD vs. 82.3 % in HTx patients, a difference that was non-statistically significant [hazard ratio (HR) 1.46; 95 % confidence interval (CI) 0.74-2.86; p = 0.27 for LVAD vs. HTx]. After group matching 1-year survival was similar between LVAD (76.9 %) and HTx (79.5 %; HR 1.15; 95 % CI 0.44-2.98; p = 0.78). Concordant data was observed at 2-year follow-up. Patients treated with LVAD as bridge-to-transplant indication (n = 22) showed a non significant better outcome compared with HTx with a 95.5 and 90.9 % survival, at 1- and 2-year follow-up, respectively. Despite worse preoperative conditions, survival is not significantly lower after LVAD than after HTx at 2-year follow-up. Given the scarce number of donors for HTx, LVAD therapy represents a valid option, potentially affecting the current allocation strategy of heart donors also in Europe.