RESUMEN
BACKGROUND: Improvement in continuous-flow left ventricular assist device (CF-LVAD) technology has translated to better outcomes for patients on CF-LVAD support as a bridge-to-transplant. However, data are lacking regarding the subset of CF-LVAD patients with renal failure awaiting simultaneous heart-kidney transplant (HKTx). We sought to better understand the characteristics and outcomes of patients in this group. METHODS: The United Network for Organ Sharing (UNOS) database was used to identify adult patients listed for heart transplant (HTx) or HKTx from January 1, 2009 to March 31, 2017. Patients were followed from time on waitlist to either removal from waitlist or transplantation. Demographic and clinical data for HTx and HKTx patients were assessed. Kaplan-Meier analysis assessed waitlist and post-transplant survival. For waitlisted patients, both death and removal from the waitlist due to deteriorating medical condition were considered events. RESULTS: Overall, 26 638 patients registered for transplant were analyzed. 25 111 (94%) were listed for HTx, and 1527 (6%) for HKTx. 7683 (29%) patients listed for HTx had CF-LVAD support. For those listed for HKTx, 441 (28%) underwent dialysis alone, 256 (17%) had CF-LVAD support alone, and 85 (6%) were treated with both CF-LVAD and dialysis. 15 567 (58%) underwent HTx, and 621 (2%) underwent HKTx. In these groups, post-transplant survival was similar (p = 0.06). Patients listed for HKTx treated with both dialysis and CF-LVAD had significantly worse waitlist survival compared to HKTx recipients (p < 0.001). CONCLUSION: Post-transplant survival is comparable between HTx and HKTx, and early survival is similar between HTx patients and those listed for HTx with CF-LVAD support. However, outcomes on the waitlist for HKTx in CF-LVAD patients on dialysis is significantly worse compared to HKTx recipients. This highlights the need to better account for this patient population when allocating organs.
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Insuficiencia Cardíaca , Trasplante de Corazón , Corazón Auxiliar , Trasplante de Riñón , Adulto , Humanos , Trasplante de Riñón/efectos adversos , Insuficiencia Cardíaca/cirugía , Corazón Auxiliar/efectos adversos , Resultado del Tratamiento , Trasplante de Corazón/efectos adversos , Estudios RetrospectivosRESUMEN
Percutaneous biventricular assist devices (BiVAD) are a recently developed treatment option for severe cardiogenic shock. This systematic review sought to identify indications and outcomes of patients placed on percutaneous BiVAD support. An electronic search was performed to identify all appropriate studies utilizing a percutaneous BiVAD configuration. Fifteen studies comprising of 20 patients were identified. Individual patient survival and outcomes data were combined for statistical analysis. All 20 patients were supported with a microaxial LVAD, 12/20 (60%) of those patients were supported with a microaxial (RMA) right ventricular assist device (RVAD), and the remaining 8/20 (40%) patients were supported with a centrifugal extracorporeal RVAD (RCF). All patients presented with cardiogenic shock, and of these, 12/20 (60%) presented with a non-ischemic etiology vs 8/20 (40%) with ischemic disease. For the RMA group, RVAD support was significantly longer [RMA 5 (IQR 4-7) days vs RCF 1 (IQR 1-2) days, p = 0.03]. Intravascular hemolysis post-BiVAD occurred in three patients (27.3%) [RMA 3 (33.3%) vs RCF 0 (0%), p = 0.94]. Five patients received a durable left ventricular assist device, one patient received a total artificial heart, and one patient underwent a heart transplantation. Estimated 30-day mortality was 15.0%, and 78.6% were discharged alive. Both strategies for percutaneous BiVAD support appear to be viable options for severe cardiogenic shock.
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Insuficiencia Cardíaca , Corazón Auxiliar , Insuficiencia Cardíaca/cirugía , Corazón Auxiliar/efectos adversos , Humanos , Estudios Retrospectivos , Choque Cardiogénico/etiología , Choque Cardiogénico/terapia , Resultado del TratamientoRESUMEN
STUDY: There is no widely accepted donor to recipient size-match metric to predict outcomes in cardiac transplant. The predictive ability of size-match metrics has not been studied when recipients are stratified by heart failure etiology. We sought to assess the performance of commonly used size metrics to predict survival after heart transplant, accounting for restrictive versus non-restrictive pathology. METHODS: The UNOS registry was queried from 2000 to 2017 for all primary isolated heart transplants. Donor-recipient ratios were calculated for commonly used size metrics and their association with survival was assessed using continuous, nonlinear analysis. RESULTS: 29 817 patients were identified. Height (P < .001), predicted heart mass (PHM) (P = .003), ideal body weight (IBW) (P < .001) and body mass index (BMI) (P = .003) ratios were significantly associated with survival, while weight and body surface area (BSA) ratios were not. When stratified, only BMI ratio retained significance for both restrictive (P = .051) and non-restrictive (P = .003) subsets. Recipients with restrictive etiology had increased risk of mortality with both a lower and higher BMI ratio. CONCLUSIONS: While many metrics show association with survival in the non-restrictive subset, BMI is the only metric that retains significance in the restrictive subset. Recipients with restrictive and non-restrictive etiologies of heart failure tolerate size mismatch differently.
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Insuficiencia Cardíaca , Trasplante de Corazón , Obtención de Tejidos y Órganos , Benchmarking , Supervivencia de Injerto , Insuficiencia Cardíaca/cirugía , Trasplante de Corazón/efectos adversos , Humanos , Tamaño de los Órganos , Estudios Retrospectivos , Donantes de TejidosRESUMEN
BACKGROUND: Major airway surgery can pose a complex problem to perioperative central airway management. Adjuncts to advanced ventilation strategies have included cardiopulmonary bypass, veno-arterial, or veno-venous extracorporeal life support. We performed a systematic review to assess the existing evidence utilizing these strategies. METHODS: An electronic search was conducted to identify studies written in English reporting the use of extracorporeal life support (ECLS) during central airway surgery. Thirty-six articles consisting of 78 patients were selected and patient-level data were analyzed. RESULTS: Median patient age was 47 [IQR: 34-53] and 59.0% (46/78) were male. Indications for surgery included central airway or mediastinal cancer in 57.7% (45/78), lesion or injury in 15.4% (12/78), and stenosis in 12.8% (10/78). Support was initiated pre-operatively in 9.9% (7/71) and at the time of induction in 55.3% (42/76). It was most commonly used at the time of tracheal resection/repair [93.2% (68/73)], intubation of the tracheal stump [94.4% (68/72)], and re-anastomosis [94.2% (65/69)]; 13.7% (10/73) patients were supported post-operatively. The most commonly performed surgery was tracheal repair or resection in 70.3% (52/74). Median hospital stay was 12 [8, 25] days and in-hospital mortality was 7.9% (6/76). There was no significant difference in survival between the three groups (p = .54). CONCLUSIONS: Extracorporeal membrane oxygenation offers versatility in timing, surgical approach, and ECLS runtime that makes it a viable addition to the surgical armamentarium for treating complex central airway pathologies.
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Manejo de la Vía Aérea/métodos , Puente Cardiopulmonar , Oxigenación por Membrana Extracorpórea , Sistema Respiratorio/cirugía , HumanosRESUMEN
INTRODUCTION: Extracorporeal carbon dioxide removal (ECCO2 R) provides respiratory support to patients suffering from hypercapnic respiratory failure by utilizing an extracorporeal shunt and gas exchange membrane to remove CO2 from either the venous (VV-ECCO2 R) or arterial (AV-ECCO2 R) system before return into the venous site. AV-ECCO2 R relies on the patient's native cardiac function to generate pressures needed to deliver blood through the extracorporeal circuit. VV-ECCO2 R utilizes a mechanical pump and can be used to treat patients with inadequate native cardiac function. We sought to evaluate the existing evidence comparing the subgroups of patients supported on VV and AV-ECCO2 R devices. METHODS: A literature search was performed to identify all relevant studies published between 2000 and 2019. Demographic information, medical indications, perioperative variables, and clinical outcomes were extracted for systematic review and meta-analysis. RESULTS: Twenty-five studies including 826 patients were reviewed. 60% of patients (497/826) were supported on VV-ECCO2 R. The most frequent indications were acute respiratory distress syndrome (ARDS) [69%, (95%CI: 53%-82%)] and chronic obstructive pulmonary disease (COPD) [49%, (95%CI: 37%-60%)]. ICU length of stay was significantly shorter in patients supported on VV-ECCO2 R compared to AV-ECCO2 R [15 (95%CI: 7-23) vs. 42 (95%CI: 17-67) days, p = 0.05]. In-hospital mortality was not significantly different [27% (95%CI: 18%-38%) vs. 36% (95%CI: 24%-51%), p = 0.26]. CONCLUSION: Both VV and AV-ECCO2 R provided clinically meaningful CO2 removal with comparable mortality.
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Síndrome de Dificultad Respiratoria , Insuficiencia Respiratoria , Dióxido de Carbono , Circulación Extracorporea , Humanos , Respiración Artificial , Insuficiencia Respiratoria/terapiaRESUMEN
BACKGROUND: Implantable cardioverter defibrillator (ICD) and permanent pacemaker (PPM) lead placement may worsen or result in tricuspid regurgitation (TR). While the association between lead placement and the incidence of TR has been established, current understanding of this problem remains incomplete. This systematic review and meta-analysis sought to pool the existing evidence to better understand the occurrence and severity of TR associated with cardiac implantable electrical device (CIED) insertion. METHODS: An electronic search was performed to identify all relevant studies published from 2000 to 2018. Overall, 15 studies were selected for the analysis comprising 4019 patients with data reported on TR development following ICD or PPM lead placement. Demographic information, perioperative clinical variables, and clinical outcome measures, including pre and postoperative echocardiographic TR grade changes, were extracted and pooled for systematic review. RESULTS: Mean patient age was 69 years [95% CI: 64.62-73.59], and 63% [95% CI: 57-68] were male. Devices implanted included ICD in 57% [95%CI: 43-70] and PPM in 41% [95%CI: 31-52]. The most common indications for pacemaker implantation were sick sinus syndrome in 22% [95% CI: 22-37] and AV block in 21% [95%CI:12-34. The commonest indications for ICD implantation were primary and secondary prevention of sudden cardiac death. Atrial fibrillation was present in 37% [95%CI: 28-46] and congestive heart failure in 15% [95%CI: 2-57]. Baseline distribution of TR grades were as follows: grade 0/1 TR in 89% [95%CI: 82-93], grade 2 TR in 8% [95%CI: 5-13], grade 3 TR in 2% [95%CI: 0-7] and grade 4 TR in 2% [95%CI: 1-4]. Post-procedure, grade 0/ 1 TR decreased to 68% [95% CI: 51-81] (p < 0.01), grade 2 TR increased to 21% [15-28] (p < 0.01), grade 3 TR increased to 13% [95%CI: 5-32] (p = 0.02), and grade 4 TR increased to 7% [95%CI: 5-9] (p < 0.01). CONCLUSION: ICD and PPM lead placement is associated with increased TR post-procedure. Further studies are warranted to evaluate changes in TR grade in the long term.
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Desfibriladores Implantables/efectos adversos , Marcapaso Artificial/efectos adversos , Insuficiencia de la Válvula Tricúspide/etiología , Humanos , Factores de RiesgoRESUMEN
The ever-widening gap between organ supply and demand has resulted in an organ shortage crisis that affects patients all over the world. For decades, static cold storage (SCS) was the gold standard preservation strategy because of its simplicity and cost-effectiveness, but the rising unmet demand for donor organ transplants has prompted investigation into preservation strategies that can expand the available donor pool. Through ex vivo functional assessment of the organ prior to transplant, newer methods to preserve organs such as perfusion-based therapy can potentially expand the available organ pool. This review will explain the physiologic rationale for SCS before exploring the advantages and disadvantages associated with the two broad classes of preservation strategies that have emerged to address the crisis: hypothermic and normothermic machine perfusion. A detailed analysis of how each preservation strategy works will be provided before investigating the current status of clinical data for each preservation strategy for the kidney, liver, pancreas, heart, and lung. For some organs there is robust data to support the use of machine perfusion technologies over SCS, and in others the data are less clear. Nonetheless, machine perfusion technologies represent an exciting frontier in organ preservation research and will remain a crucial component of closing the gap between organ supply and recipient demand.
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Preservación de Órganos/métodos , Perfusión/métodos , Trasplantes , Humanos , Refrigeración , Daño por Reperfusión/prevención & controlRESUMEN
Modern extracorporeal life-support (ECLS) technology has been successfully utilized to treat patients with diffuse alveolar damage (DAD) and diffuse alveolar hemorrhage (DAH); however, reports in the literature remain scarce. We sought to pool existing evidence to better characterize ECLS use in these patients. An electronic search was conducted to identify all studies in the English literature reporting the use of ECLS for DAD/DAH. Thirty-two articles consisting of 38 patients were selected, and patient-level data were extracted and pooled for analysis. Median patient age was 36 [IQR: 27, 48] years, and the majority (63.2%) were female. Most common etiological factors included granulomatosis with polyangiitis (8/38, 21.1%), systemic lupus erythematosus (8/38, 21.1%), Goodpasture's syndrome (4/38, 10.5%), and microscopic polyangiitis (4/38, 10.5%). Immunologic markers included anti-neutrophil cytoplasmic antibody (ANCA) in 15/38 (39.5%), anti-nuclear antibody (ANA) in 6/38 (15.8%), and anti-glomerular basement membrane (anti-GBM) antibodies in 4/38 (10.5%). DAH was present in 32/38 (84.2%) of cases and DAD without evidence of DAH was present in 6/38 (15.8%) of cases. ECLS strategies included extracorporeal membrane oxygenation of veno-venous type (VV-ECMO) in 28/38 (73.7%), veno-arterial type (VA-ECMO) in 5/38 (13.2%), and one case of right ventricular assist device with oxygenator (RVAD-ECMO). Heparin was utilized in 18/38 (47.4%) of cases with no difference in use between DAH versus no DAH (P = .46) or VA- versus VV-ECLS (P = 1). Median duration of ECLS was 10 [5, 14] days. Pre- versus post-ECLS comparison of blood gases showed improvement in median PaO2 (49 [45, 59] mm Hg vs. 80 [70, 99] mm Hg, P < .001), PaO2:FiO2 ratio (48.2 [41.4, 54.8] vs. 182.0 [149.4, 212.2], P < .01), and pulse oximetry values (76% [72, 80] vs. 96% [94, 97], P = .086). Overall, 94.7% (36/38) of patients survived to decannulation while 30-day mortality was 10.5% (4/38) with no differences between VA- and VV-ECMO (P = 1 and P = .94, respectively). DAD/DAH occurs in a younger, predominantly female population, and tends to be associated with systemic autoimmune processes. ECLS, independent of its type, appears to result in favorable short-term survival.
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Oxigenación por Membrana Extracorpórea , Hemorragia/terapia , Enfermedades Pulmonares/terapia , Alveolos Pulmonares/patología , HumanosRESUMEN
Despite improved outcomes of modern continuous-flow left ventricular assist devices (CF-LVADs), device exchange is still needed for various indications. While the majority of CF-LVADs are exchanged to the same model, exchange to a different pump model is occasionally warranted. In this meta-analysis, we sought to consolidate the existing evidence to better elucidate the indications and outcomes in these cases. A comprehensive systematic search of adult patient cohorts who underwent CF-LVAD exchange to a different CF-LVAD model was performed. Study-level data from 10 studies comprising 98 patients were extracted and pooled for analysis. Mean patient age was 58 (95% CI: 48-65) and 81% were male. Indication for initial CF-LVAD was ischemic cardiomyopathy in 45% (34-57). Initial device was HeartMate II LVAD (HMII) in 93 (94.9%) and HeartWare HVAD (HW) in 5 (5.1%) patients. After mean CF-LVAD support time of 18.8 (15.2-22.4) months, exchange indications included thrombosis in 71% (43-89), infection in 21% (8-47) and device malfunction in 12% (7-21). HMII to HW exchange occurred in 53 (54.1%) patients, HMII to HeartMate III (HM3) in 32 (32.7%), and HM II to either HW or HM3 in 13 (13.2%) patients. Postoperatively, right ventricular assist device was required in 16% (8-32). Overall, 20% (8-40) of patients experienced a stroke, while HW patients had a significantly higher stroke incidence than HM3 patients (HW: 21% (8-47) vs. HM3: 5% (1-24), P < .01). Overall 30-day mortality was 10% (6-17), while HW had a significantly worse 30-day mortality than HM3 (HW: 13% (7-24) vs. HM3: 5% (1-24), P = .03). Following device exchange from a different CF-LVAD model, HM3 is associated with lower stroke and higher survival when compared to HW.
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Remoción de Dispositivos , Corazón Auxiliar/efectos adversos , Falla de Equipo , Insuficiencia Cardíaca/terapia , Humanos , Infecciones/complicaciones , Accidente Cerebrovascular/etiología , Trombosis/complicacionesRESUMEN
Stenosis in the continuous-flow left ventricular assist device (CF-LVAD) outflow graft is caused by various factors. We discuss indications for percutaneous intervention of outflow graft complications and evaluate the use of this treatment in re-establishing adequate CF-LVAD flow. An electronic search was performed to identify all studies in the English literature reporting CF-LVAD outflow graft stenting. Twenty-one studies consisting of 26 patients were included. Patient-level data were extracted for statistical analysis. Median patient age was 59 years [45.8-67.0] and 65.4% (17/26) were male. 58.3% (14/24) of patients had HeartWare HVAD, 37.5% (9/24) had HeartMate II LVAD, and 4.2% (1/24) had HeartMate III LVAS. Median time from device placement to outflow graft stenting was 24.0 months [7.8-30.4]. 76.9% of patients (20/26) presented with heart failure. Complications of the CF-LVAD outflow graft included thrombosis in nine patients (34.6%), stenosis in nine patients (34.6%), kinking in three patients (11.5%), pseudoaneurysm in one patient (3.8%), external graft compression in one patient (3.8%), and bronchial-arterial fistula in one patient (3.6%). Immediate flow improvement occurred in 23/26 patients (88.5%), with the remaining 11.5% (3/26) requiring additional procedures. Pre- and post-intervention flows were 2.9 L/min [2.0-3.5] and 4.7 L/min [4.1-4.8] respectively (p = 0.01). Of patients, 96.2% (25/26) were discharged with a median time to discharge of 4 days [3.0-5.0]. The 30-day mortality was 6.7% (1/15). Overall mortality during the median follow-up of 90 days was 9.5% (2/21). Outflow graft stenting appears to effectively alleviate CF-LVAD outflow graft obstruction and is associated with low overall mortality.
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Insuficiencia Cardíaca/cirugía , Ventrículos Cardíacos/fisiopatología , Corazón Auxiliar/efectos adversos , Complicaciones Posoperatorias/mortalidad , Stents/efectos adversos , Constricción Patológica/mortalidad , Salud Global , Insuficiencia Cardíaca/fisiopatología , Humanos , Falla de Prótesis , Tasa de Supervivencia/tendenciasRESUMEN
Based on Organ Procurement and Transplantation Network data as of December 2019, more than 113 000 patients require an organ transplantation, yet, over the course of this past year, only 36 000 patients received a transplant. This discrepancy between those that need a donor organ and those that receive one remains one of medicine's biggest challenges. Multiple solutions, both biologic and artificial, have been proposed to mitigate this difference. One of the most promising approaches to generate bioartificial organs for transplantation involves re-seeding decellularized scaffolds with appropriate cells. Decellularization involves physical, chemical, or biological methods that typically require intimate contact of various decellularization solutions with each cell. Consequently, conventional submersion decellularization has been limited to simple tissues such as heart valves. The invention of perfusion decellularization was a breakthrough that allowed the generation of tissue-engineered scaffolds from tissues with higher structural organization and entire organs. Such scaffolds are composed of a myriad of extracellular matrix (ECM) components that include collagen, elastin, proteoglycans, and glycoproteins. Together, these components allow the scaffolds to fulfill specialized functions, such as structural functions as well as biological functions including the regulation of cellular processes and extracellular molecules. These specialized functions of decellularized scaffolds can increasingly be harnessed for applications in tissue engineering.
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Órganos Bioartificiales , Trasplante de Órganos/tendencias , Ingeniería de Tejidos/métodos , Andamios del Tejido , Obtención de Tejidos y Órganos/provisión & distribución , Animales , Humanos , Modelos Animales , Trasplante de Órganos/estadística & datos numéricosRESUMEN
In patients with biventricular heart failure or refractory right heart failure following HeartWare HVAD placement, off-label placement of a right-sided HeartWare HVAD has been described both in the right ventricular (RV) and right atrial (RA) positions. We sought to evaluate and compare the outcomes of right-sided HeartWare HVAD using the RA versus RV approach. An electronic search was performed in the English literature to identify all reports of left- and right-heart support with HeartWare HVAD. Of the 1,288 articles identified, 13 articles with 56 cases met inclusion criteria. Patient-level data were extracted and analyzed. The median patient age was 52 years (IQR 33.0-59.0) and 40/50 (80.0%) were male. Overall, 21/56 patients (37.5%) had RA HVAD, while 35/56 (62.5%) had RV HVAD. Most underwent concomitant HVAD placement [RA: 17/21 (81.0%) vs. RV: 31/35 (88.6%), P = .69]. In those who did not, the median time between left and right HVAD was 10 days (IQR 7-14) for RA HVAD and 12 days (IQR 8-30) for RV HVAD (P = .77). The median time of support was 351 days (IQR 136-626) for RA HVAD compared to 135 days (IQR 61-244) for RV HVAD (P = .02). Pump thrombosis occurred at a similar rate [RA: 3/10 (30.0%) vs. RV: 6/20 (30.0%), P = 1], as did GI bleeding [RA: 10/35 (28.6%) vs. RV: 5/21 (23.8%), P = .94] during the follow-up time period. Kaplan-Meier analysis when censored for transplant showed higher survival with RA HVAD compared to RV HVAD (P = .036), with an estimated survival at 1 year of 91.7% (95% CI 77.3-100.0) in RA HVAD versus 66.2% (95% CI 48.9-89.6) for RV HVAD. RA HVAD appears to be a viable option for durable right-sided support with outcomes at least comparable to RV HVAD.
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Insuficiencia Cardíaca/cirugía , Corazón Auxiliar , Implantación de Prótesis/métodos , Disfunción Ventricular Izquierda/complicaciones , Disfunción Ventricular Derecha/complicaciones , Atrios Cardíacos/cirugía , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/mortalidad , Ventrículos Cardíacos/cirugía , Humanos , Estimación de Kaplan-Meier , Implantación de Prótesis/instrumentación , Resultado del Tratamiento , Disfunción Ventricular Izquierda/mortalidad , Disfunción Ventricular Izquierda/cirugía , Disfunción Ventricular Derecha/mortalidad , Disfunción Ventricular Derecha/cirugíaRESUMEN
BACKGROUND AND AIM OF THE STUDY: Ventricular septal defect (VSD) following myocardial infarction (MI) is a relatively infrequent complication with high mortality. We sought to investigate the effect of concomitant coronary artery bypass graft (CABG) on outcomes following post-MI VSD repair. METHODS: Electronic search was performed to identify all relevant studies published from 2000 to 2018. Sixty-seven studies were selected for the analysis comprising 2174 patients with post-MI VSD. Demographic information, perioperative variables, and outcomes including survival data were extracted and pooled for systematic review and meta-analysis. RESULTS: Single-vessel disease was most common (47%, 95% confidence interval [CI], 42-52), left anterior descending coronary artery was the most commonly involved vessel (55%, 95% CI, 46-63), and anterior wall was the most commonly affected territory (57%, 95% CI, 51-63). Concomitant CABG was performed in 52% (95% CI, 46-57) of patients. Of these, infarcted territory was re-vascularized in 54% (95% CI, 23-82). A residual/recurrent shunt was present in 29% (95% CI, 24-34) of patients. Of these, surgical repair was performed in 35% (95% CI, 28-41) and transcatheter repair in 11% (95% CI, 6-21). Thirty-day mortality was 30% (95% CI, 26-35) in patients who had preoperative coronary angiogram, and 58% (95% CI, 43-71) in those who did not (P < .01). No significant survival difference observed between those who had concomitant CABG vs those without CABG. CONCLUSIONS: Concomitant CABG did not have a significant effect on survival following VSD repair. Revascularization should be weighed against the risks associated with prolonged cardiopulmonary bypass.
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Cateterismo Cardíaco/métodos , Procedimientos Quirúrgicos Cardíacos/métodos , Puente de Arteria Coronaria , Defectos del Tabique Interventricular/cirugía , Puente Cardiopulmonar/efectos adversos , Femenino , Defectos del Tabique Interventricular/etiología , Defectos del Tabique Interventricular/mortalidad , Humanos , Masculino , Infarto del Miocardio/complicaciones , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Glucagon-like peptide 1 (GLP-1) and glucagon share the same precursor molecule proglucagon, but each arises from a distinct posttranslational process in a tissue-specific manner. Recently, it has been shown that GLP-1 is co-expressed with glucagon in pancreatic islet cells. This study was aimed to investigate the progressive changes of GLP-1 versus glucagon production in pancreatic islets during the course of diabetes development. METHODS: Both type 1 (non-obese diabetes mice) and type 2 (db/db mice) diabetes models were employed in this study. The mice were monitored closely for their diabetes progression and were sacrificed at different stages according to their blood glucose levels. GLP-1 and glucagon expression in the pancreatic islets was examined using immunohistochemistry assays. Quantitative analysis was performed to evaluate the significance of the changes. RESULTS: The ratio of GLP-1-expressing cells to glucagon-expressing cells in the islets showed significant, progressive increase with the development of diabetes in db/db mice. The increase of GLP-1 expression was in agreement with the upregulation of PC1/3 expression in these cells. Interestingly, intra-islet GLP-1 expression was not significantly changed during the development of type 1 diabetes in non-obese diabetes mice. CONCLUSIONS: The study demonstrated that GLP-1 was progressively upregulated in pancreatic islets during type 2 diabetes development. In addition, the data suggest clear differences in intra-islet GLP-1 production between type 1 and type 2 diabetes developments. These differences may have an effect on the clinical and pathophysiological processes of these diseases and may be a target for therapeutic approaches.
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Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Péptido 1 Similar al Glucagón/metabolismo , Islotes Pancreáticos/metabolismo , Estado Prediabético/metabolismo , Algoritmos , Animales , Diabetes Mellitus Tipo 1/patología , Diabetes Mellitus Tipo 1/fisiopatología , Diabetes Mellitus Tipo 2/patología , Diabetes Mellitus Tipo 2/fisiopatología , Progresión de la Enfermedad , Femenino , Glucagón/metabolismo , Células Secretoras de Glucagón/metabolismo , Células Secretoras de Glucagón/patología , Inmunohistoquímica , Islotes Pancreáticos/patología , Islotes Pancreáticos/fisiopatología , Masculino , Ratones Endogámicos C57BL , Ratones Endogámicos NOD , Ratones Mutantes , Estado Prediabético/patología , Estado Prediabético/fisiopatología , Proproteína Convertasa 1/metabolismo , Regulación hacia ArribaRESUMEN
Background: Lung volume reduction (LVR) and lung transplantation (LTx) have been used in different populations of chronic obstructive pulmonary disease (COPD) patients. To date, comparative study of LVR and LTx has not been performed. We sought to address this gap by pooling the existing evidence in the literature. Methods: An electronic search was performed to identify all prospective studies on LVR and LTx published since 2000. Baseline characteristics, perioperative variables, and clinical outcomes were extracted and pooled for meta-analysis. Results: The analysis included 65 prospective studies comprising 3,671 patients [LTx: 15 studies (n=1,445), LVR: 50 studies (n=2,226)]. Mean age was 60 [95% confidence interval (CI): 58-62] years and comparable between the two groups. Females were 51% (95% CI: 30-71%) in the LTx group vs. 28% (95% CI: 21-36%) in LVR group (P=0.05). Baseline 6-minute walk test (6MWT) and pulmonary function tests were comparable except for the forced expiratory volume in 1 second (FEV1), which was lower in the LTx group [21.8% (95% CI: 16.8-26.7%) vs. 27.3% (95% CI: 25.5-29.2%), P=0.04]. Postoperatively, both groups experienced improved FEV1, however post-LTx FEV1 was significantly higher than post-LVR FEV1 [54.9% (95% CI: 41.4-68.4%) vs. 32.5% (95% CI: 30.1-34.8%), P<0.01]. 6MWT was also improved after both procedures [LTx: 212.9 (95% CI: 119.0-306.9) to 454.4 m (95% CI: 334.7-574.2), P<0.01; LVR: 286 (95% CI: 270.2-301.9) to 409.1 m (95% CI: 392.1-426.0), P<0.01], however, with no significant difference between the groups. Pooled survival over time showed no significant difference between the groups. Conclusions: LTx results in better FEV1 but otherwise has comparable outcomes to LVR.
RESUMEN
INTRODUCTION: Patients on continuous flow left ventricular assist devices (CF-LVADs) often require CF-LVAD exchange. The purpose of this study was to investigate the incidence of infection following CF-LVAD exchange performed for non-infectious indications. METHODS: An electronic literature search was performed to identify all studies of patients undergoing CF-LVAD exchange for pump thrombosis or device malfunction. Of 2,698 articles identified, 6 studies with 81 total patients met the inclusion criteria. Cohort-level data were pooled for meta-analysis. RESULTS: Mean patient age was 60 years (95% CI: 41-78), and 74% were male (95% CI: 61-84). Pump thrombosis was the most common indication for exchange in 70% of patients (95% CI: 47-86). Other indications were driveline fracture and electrical malfunction in 21% (95% CI: 5-56) and 12% (95% CI: 4-33) of patients, respectively. Prior to exchange, 95% of patients were on HeartMate II (HM2) LVADs (95% CI: 86-98) and average duration of support for these patients was 27.1 months (95% CI: 9.3-44.8). The majority were placed on a HM2 following exchange (88% (95% CI: 45-98)) versus HM3 (12% (95% CI: 2-55)). Follow-up was an average of 16.4 months (95% CI: 6.8-26.0). Following exchange, 16 of 81 patients developed infection, with pooled mean incidence of 24% (95% CI: 14-38). 30-day mortality was 14% (95% CI: 7-26). Survival at follow-up was 65% (95% CI: 52-76). CONCLUSIONS: Infection following CF-LVAD exchange can occur at rates higher than those observed with primary implantation; therefore, effective strategies need to implemented early and consistently to help lower infections rates and help improve outcomes following exchange.