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OBJECTIVE: Oxygen consumption (VO2), carbon dioxide generation (VCO2), and respiratory quotient (RQ), which is the ratio of VO2 to VCO2, are critical indicators of human metabolism. To seek a link between the patient's metabolism and pathophysiology of critical illness, we investigated the correlation of these values with mortality in critical care patients. METHODS: This was a prospective, observational study conducted at a suburban, quaternary care teaching hospital. Age 18 years or older healthy volunteers and patients who underwent mechanical ventilation were enrolled. A high-fidelity automation device, which accuracy is equivalent to the gold standard Douglas Bag technique, was used to measure VO2, VCO2, and RQ at a wide range of fraction of inspired oxygen (FIO2). RESULTS: We included a total of 21 subjects including 8 post-cardiothoracic surgery patients, 7 intensive care patients, 3 patients from the emergency room, and 3 healthy volunteers. This study included 10 critical care patients, whose metabolic measurements were performed in the ER and ICU, and 6 died. VO2, VCO2, and RQ of survivors were 282 +/- 95 mL/min, 202 +/- 81 mL/min, and 0.70 +/- 0.10, and those of non-survivors were 240 +/- 87 mL/min, 140 +/- 66 mL/min, and 0.57 +/- 0.08 (p = 0.34, p = 0.10, and p < 0.01), respectively. The difference of RQ was statistically significant (p < 0.01) and it remained significant when the subjects with FIO2 < 0.5 were excluded (p < 0.05). CONCLUSIONS: Low RQ correlated with high mortality, which may potentially indicate a decompensation of the oxygen metabolism in critically ill patients.
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Pulmão , Respiração Artificial , Humanos , Adolescente , Estudos Prospectivos , Calorimetria Indireta/métodos , Consumo de Oxigênio , Dióxido de Carbono/metabolismo , Estado Terminal/terapia , OxigênioRESUMO
In this case report, we describe the clinical course of a complicated transplant renal artery (TRA) pseudoaneurysm, clinically featured by gross and massive hematuria one month after a kidney transplant was performed on a 50 year-old male patient. TRA pseudoaneurysm is a rare but potentially life-threatening complication that may result in bleeding, infection, graft dysfunction/loss, lower limb ischemia/loss, hemorrhagic shock, and death. TRA pseudoaneurysm treatment remains challenging as it needs to be tailored to the patient characteristics including hemodynamic stability, graft function, anatomy, presentation, and pseudoaneurysm features. This publication discusses the clinical scenario of massive gross hematuria that derived from a retroperitoneal hematoma which originated from an actively bleeding TRA pseudoaneurysm. This case highlights the combined approach of endovascular stent placement and subsequent transplant nephrectomy as a last resort in the management of intractable bleeding from a complicated TRA pseudoaneurysm. To the best of our knowledge, this is the first published case report of an actively bleeding TRA anastomotic pseudoaneurysm that caused a massive retroperitoneal bleed that in turn evacuated via the bladder after disrupting the ureter-to-bladder anastomosis. A temporizing hemostatic arterial stent placed percutaneously allowed for a safer and controlled emergency transplant nephrectomy.
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This case study describes a 45-year-old Caucasian male with a past medical history of obesity, hypertension, and non-insulin-dependent diabetes mellitus, who in the setting of coronavirus disease 2019 (COVID-19) pneumonia, developed portal vein thrombosis (PVT) presenting as an acute abdomen after hospital discharge from a cholecystitis episode. PVT is a very infrequent thromboembolic condition, classically occurring in patients with systemic conditions such as cirrhosis, malignancy, pancreatitis, diverticulitis, autoimmunity, and thrombophilia. PVT can cause serious complications, such as intestinal infarction, or even death, if not promptly treated. Due to the limited number of reports in the literature describing PVT in the COVID-19 setting, its prevalence, natural history, mechanism, and precise clinical features remain unknown. Therefore, clinical suspicion should be high for PVT, in any COVID-19 patient who presents with abdominal pain or associated signs and symptoms. To the best of our knowledge, this is the first report of COVID-19-associated PVT causing extensive thrombosis in the portal vein and its right branch, occurring in the setting of early-stage cirrhosis after a preceding episode of cholecystitis.
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OBJECTIVE: Using a system, which accuracy is equivalent to the gold standard Douglas Bag (DB) technique for measuring oxygen consumption (VO2), carbon dioxide generation (VCO2), and respiratory quotient (RQ), we aimed to continuously measure these metabolic indicators and compare the values between post-cardiothoracic surgery and critical care patients. METHODS: This was a prospective, observational study conducted at a suburban, quaternary care teaching hospital. Age 18 years or older patients who underwent mechanical ventilation were enrolled. RESULTS: We included 4 post-surgery and 6 critical care patients. Of those, 3 critical care patients died. The longest measurement reached to 12 h and 15 min and 50 cycles of repeat measurements were performed. VO2 of the post-surgery patients were 234 ± 14, 262 ± 27, 212 ± 16, and 192 ± 20 mL/min, and those of critical care patients were 122 ± 20, 189 ± 9, 191 ± 7, 191 ± 24, 212 ± 12, and 135 ± 21 mL/min, respectively. The value of VO2 was more variable in the post-surgery patients and the range of each patient was 44, 126, 71, and 67, respectively. SOFA scores were higher in non-survivors and there were negative correlations of RQ with SOFA. CONCLUSIONS: We developed an accurate system that enables continuous and repeat measurements of VO2, VCO2, and RQ. Critical care patients may have less activity in metabolism represented by less variable values of VO2 and VCO2 over time as compared to those of post-cardiothoracic surgery patients. Additionally, an alteration of these values may mean a systemic distinction of the metabolism of critically ill patients.
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Cuidados Críticos , Consumo de Oxigênio , Humanos , Adolescente , Estudos Prospectivos , Calorimetria Indireta/métodos , Respiração Artificial , Dióxido de Carbono/metabolismoRESUMO
In this case study, we describe a 25-year-old male who was admitted due to a severe traumatic brain injury, requiring invasive intracranial pressure monitoring. At 48 hours posttrauma, he developed intracranial hypertension refractory to medical treatment without tomographic changes in the brain. Subsequently, intra-abdominal hypertension and tomographic signs of abdominal surgical pathology were observed. An exploratory laparotomy was performed with an intraoperative diagnosis of acute mesenteric ischemia. After surgical intervention for the abdominal pathology, intracranial pressure was restored to physiological values with a favorable recovery of the patient. In this report, the relationship between intracranial pressure and intra-abdominal pressure is discussed, highlighting the delicate association between the brain, abdomen, and thorax. Measures should be taken to avoid increases in intra-abdominal pressure in neurocritical patients. When treating intracranial hypertension refractory to conventional measures, abdominal causes and multiple compartment syndrome must be considered. The cranial compartment has physiological interdependence with other body compartments, where one can be modified by variations from another, giving rise to the concept of multiple compartment syndrome. Understanding this relationship is fundamental for a comprehensive approach of the neurocritical patient. To the best of our knowledge, this is the first report of a comatose patient post-traumatic brain injury, who developed medically unresponsive intracranial hypertension secondary to acute mesenteric ischemia, in which surgical resolution of intra-abdominal pathology resulted in intracranial pressure normalization and restitutio ad integrum of neurological status.
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While social justice is a pillar that society seeks to uphold, in the area of organ transplantation, social justice, equity, and inclusion fail in the unbefriended and undomiciled population. Due to lack of social support of the homeless population, such status often renders these individuals ineligible to be organ recipients. Though it can be argued that organ donation by an unbefriended, undomciled patient benefits the greater good, there is clear inequity in the fact that homeless individuals are denied transplants due to inadequate social support. To illustrate such social breakdown, we describe two unbefriended, undomiciled patients brought to our hospitals by emergency services with diagnoses of intracerebral haemorrhage that progressed to brain death. This proposal represents a call to action to remediate the broken system: how the inherent inequity in organ donation by unbefriended, undomiciled patients would be ethically optimized if social support systems were implemented to allow for their candidacy for organ transplantation.
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BACKGROUND: Cardiac arrest (CA) can lead to neuronal degeneration and death through various pathways, including oxidative, inflammatory, and metabolic stress. However, current neuroprotective drug therapies will typically target only one of these pathways, and most single drug attempts to correct the multiple dysregulated metabolic pathways elicited following cardiac arrest have failed to demonstrate clear benefit. Many scientists have opined on the need for novel, multidimensional approaches to the multiple metabolic disturbances after cardiac arrest. In the current study, we have developed a therapeutic cocktail that includes ten drugs capable of targeting multiple pathways of ischemia-reperfusion injury after CA. We then evaluated its effectiveness in improving neurologically favorable survival through a randomized, blind, and placebo-controlled study in rats subjected to 12 min of asphyxial CA, a severe injury model. RESULTS: 14 rats were given the cocktail and 14 received the vehicle after resuscitation. At 72 h post-resuscitation, the survival rate was 78.6% among cocktail-treated rats, which was significantly higher than the 28.6% survival rate among vehicle-treated rats (log-rank test; p = 0.006). Moreover, in cocktail-treated rats, neurological deficit scores were also improved. These survival and neurological function data suggest that our multi-drug cocktail may be a potential post-CA therapy that deserves clinical translation. CONCLUSIONS: Our findings demonstrate that, with its ability to target multiple damaging pathways, a multi-drug therapeutic cocktail offers promise both as a conceptual advance and as a specific multi-drug formulation capable of combatting neuronal degeneration and death following cardiac arrest. Clinical implementation of this therapy may improve neurologically favorable survival rates and neurological deficits in patients suffering from cardiac arrest.
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Reanimação Cardiopulmonar , Parada Cardíaca , Animais , Ratos , Reanimação Cardiopulmonar/métodos , Parada Cardíaca/complicações , Parada Cardíaca/terapia , Ratos Sprague-Dawley , RoedoresRESUMO
Organ transplantation can be associated with vascular torsions and angulations of both recipient and donor vessels. Such kinks and/or torsions of vessels can compromise the vascular integrity, obstruct inflow and/or outflow, and result in loss of the organ and/or body parts. On many occasions, mild angulations and torsions can be successfully addressed by repositioning the organ. In cases where the abnormal findings persist, maneuvers such as placing a fat pad to create a smoother curve, or even opening the peritoneum (in the case of kidney transplants) to allow for a better positioning of the organ, are associated with successful outcomes. When such torsions/angulations persist despite these approaches, further innovative tactics are required. In the current report, we propose a technique that involves longitudinally opening of a synthetic graft that is rigid enough to maintain its shape, such as a ringed polytetrafluoroethylene graft, and placing it as an external stent around the angulated/torsioned vessel. This maneuver will correct the underlying vascular compromise without having to perform any further invasive interventions, such as reimplanting the organ or resecting part of the involved vessel. Although primarily illustrated for application by describing an instance in which exostenting was applied during kidney transplantation, our approach could be applied to any vessel under many circumstances where angulations/twists are encountered. In this report, we describe the use of an external stent, also called exostenting, to correct a severe torsion/angulation of the external iliac artery in a kidney transplant recipient where all other measures were unsuccessful.
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PURPOSE: To develop a system that is equivalent to the gold standard Douglas Bag (DB) technique for measuring oxygen consumption (VÌo2), carbon dioxide generation (VÌco2), and respiratory quotient (RQ) and to validate its use in clinical settings. METHODS: This was a prospective, observational study conducted at a suburban, quaternary care teaching hospital. Healthy volunteers and patients 18 years or older who received mechanical ventilation were enrolled. FINDINGS: Data from 3 healthy volunteers and 7 patients were analyzed in this study. The interrater reliability between the automation device and DB methods were 0.999, 0.993, and 0.993 for VÌo2, VÌco2, and RQ, respectively. In healthy volunteers, mean (SD) VÌo2, VÌco2, and RQ measured by DB were 411 (100) mL/min, 288 (79) mL/min, and 0.70 (0.03) at high fraction of inspired oxygen (Fio2) and 323 (46) mL/min, 280 (45) mL/min, and 0.85 (0.05) at normal Fio2, respectively. VÌo2 was significantly higher (P < 0.05) and RQ was lower (P < 0.01) in the high Fio2 group as compared to those in the normal Fio2 group. Values measured by the automation system were 227 (31) mL/min, 141 (18) mL/min, and 0.62 (0.04) at high Fio2 and 209 (25) mL/min, 147 (18) mL/min, and 0.70 (0.06) at normal Fio2, respectively. RQ was significantly lower (P < 0.05) in the high Fio2 group as compared to the normal Fio2 group. We also successfully performed continuous and repeat measurements by using the device. The longest measurement reached 12 hours 15 minutes, including 50 cycles of repeat measurements that are equivalent to the DB technique as described above. IMPLICATIONS: We developed an automation system that enables repeat measurements of VÌo2, VÌco2, and RQ, and the accuracy was equivalent to the DB technique. High Fio2 may decrease RQ because of an increase in VÌo2.
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Oxigênio , Respiração Artificial , Humanos , Calorimetria Indireta/métodos , Reprodutibilidade dos Testes , Estudos Prospectivos , AutomaçãoRESUMO
OBJECTIVES: This study aimed to assess portal and hepatic venous volumes as related to the planning of complex liver resections and segmental liver transplant. MATERIALS AND METHODS: We analyzed 3-dimensional computed tomography of portal and hepatic vein territorial maps of 140 potential living related liver donors. Portal and hepatic vein maps were simulated both separately and in overlap (cross-mapping) to calculate inflow and outflow volumes. RESULTS: In total liver volume, the right hemiliver was always dominant (mean 64.7 ± 4.8%) and the right medial sector (mean 36.4 ± 6.8%) and segment 8 (mean 19.1 ± 4.3%) accounted for the largest volumes, whereas the left medial sector(mean 13.5 ± 3.1%) and segment 4A (mean 5.8 ± 1.8%) accounted for the smallest volumes (with exclusion of caudate lobe). The right hepatic vein was dominant for both right hemiliver and right lateral sector and had the largest drainage volume in total liver volume (mean 40.0 ± 11.2%). The left hepatic vein was dominant for both left hemiliver and left lateral sector but had the smallest drainage volume fortotal liver volume (mean 21.3 ± 5.0%). The middle hepatic vein drained 50.2 ± 12.5% of the right medial sector and 75.8 ± 15.4% of the left medial sector. In 67 cases, an accessory vein (inferior hepatic vein) drained 16.5 ± 13.2% ofthe right hemiliver, 31.4 ± 25.1% ofthe right lateral sector, 26.6 ± 23.2% of segment 7, and 37.4 ± 31.3% of segment 6. CONCLUSIONS: The portal and hepatic vein territorial anatomy was characterized by extensive individual variability. An extremely smallremnant volume (<25% of total liver volume) precluded a minority of virtual extended left and a majority of extended right hepatectomies. Left trisectionectomy was associated with risky drainage from the middle hepatic vein, extensive segment 6 remnant congestion volume in 8% of cases, and right lateral sector-favorable inferior hepatic vein large drainage pattern in 13% of livers.
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Veias Hepáticas , Fígado , Hepatectomia/métodos , Veias Hepáticas/anatomia & histologia , Veias Hepáticas/diagnóstico por imagem , Humanos , Fígado/anatomia & histologia , Fígado/diagnóstico por imagem , Fígado/cirurgia , Doadores Vivos , Veia Porta/anatomia & histologia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Stenosis proximal to transplant renal artery anastomoses are complications leading to allograft dysfunction. This study was aimed to evaluate a novel surgical approach to renal allograft revascularization, taking into consideration the length of time elapsed since transplantation. We describe an arterial bypass using a polytetrafluoroethylene (PTFE) graft from the common iliac artery (proximal to the renal artery implantation) to the external iliac artery (distal to the renal artery implantation) that allows the adequate revascularization of both the transplant kidney, as well as the lower extremity. This technique provides several advantages when compared with previously described procedures to revascularize a transplanted kidney with an iliac artery stenosis proximal to the allograft implantation site. Benefits of this technique include (1) no need to repair the stenosis, (2) no need to take down and redo the arterial anastomosis, (3) no need to perform a dissection around the renal hilum of the transplanted kidney, (4) no requirement to address the anastomosis transfer, and (5) no need to perfuse the kidney with preservation fluid at the time of repair and/or (6) avoidance of potential injury to the renal parenchyma and/or hilum during dissections. Adequate perfusion of the organ, as well as of the lower extremity was verified by serial Doppler duplex ultrasound evaluations. Hence, we describe a novel revascularization technique in instances of kidney transplant and lower extremity ischemia.
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OBJECTIVES: Primary gallbladder cancer (GBC) is the most common biliary tract cancer with poor survival despite aggressive treatment. This study aimed to investigate the trends of GBC incidence and incidence-based mortality (IBM) over the last 4 decades. MATERIALS AND METHODS: GBC cases diagnosed between 1973 and 2015 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Incidence rates, IBM rates, and annual percent changes (APCs) were calculated and stratified according to population and tumor characteristics. RESULTS: The cohort consisted of 10,792 predominantly white (81%) and female (71%) GBC patients. The overall GBC incidence decreased by 1.65% (95% confidence interval [CI]: 1.45% to 1.84%) per year since 1973, but has plateaued since 2002. IBM decreased by 1.69% (95% CI: 1.22% to 2.16%) per year from 1980 to 2015; the rate of decrease in IBM rates was lower during 1997 to 2015 (APC: -1.19%, 95% CI: -1.68% to -0.71%) compared with 1980 to 1997 (APC: -3.13%, 95% CI: -3.68% to -2.58%). CONCLUSIONS: The incidence and IBM rates of GBC have been decreasing over the last 40 years, but the decrease plateaued over the last 2 decades. The effects of treatment modalities, including laparoscopic cholecystectomy, adjuvant chemotherapy, and radiation on the incidence and IBM of GBC need to be further investigated.
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Neoplasias do Sistema Biliar , Neoplasias da Vesícula Biliar , Quimioterapia Adjuvante , Feminino , Neoplasias da Vesícula Biliar/epidemiologia , Neoplasias da Vesícula Biliar/terapia , Humanos , Incidência , Estados Unidos/epidemiologiaRESUMO
Background: Race coefficients of estimated glomerular filtration rate (eGFR) formulas may be partially responsible for racial inequality in preemptive listing for kidney transplantation. Methods: We used the Scientific Registry of Transplant Recipients database to evaluate differences in racial distribution of preemptive listing before and after application of the Modification of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) race coefficients to all preemptively listed non-Black kidney transplant candidates (eGFR modulation). Odds of preemptive listing were calculated by race, with Black as the reference before and after eGFR modulation. Variables known to influence preemptive listing were included in the model. Results: Among 385 087 kidney-alone transplant candidates from 1 January 2010 to 2 December 2020, 118 329 (30.7%) candidates were identified as preemptively listed (71.7% White, 19% Black, 7.8% Asian, 0.6% multi-racial, 0.6% Native American and 0.3% Pacific Islander). After eGFR modulation, non-Black patients with an eGFR ≥20 mL/min/1.73 m2 were removed. Compared with Black candidates, the adjusted odds of preemptive listing for White candidates decreased from 2.01 [95% confidence interval (95% CI) 1.78-2.26] before eGFR modulation to 1.18 (95% CI 1.0-1.39; P = 0.046) with the MDRD and 1.37 (95% CI 1.18-1.58) with the CKD-EPI equations after adjusting for race coefficients. Conclusions: Removing race coefficients in GFR estimation formulas may result in a more equitable distribution of Black candidates listed earlier on a preemptive basis.
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Existing literature has demonstrated the significant relationship between race and kidney transplant outcomes; however, there are conflicting and limited data on the influence of donor race or donor-recipient race-matching on pediatric kidney transplant outcomes. Methods: Analysis included kidney-only transplant recipients between ages 2 and 17 from 2000 to 2017 enrolled in the Organ Procurement and Transplantation Network and their associated donors. Multivariable regression models were used to compare outcomes by donor race and donor-recipient race-matched status. Results: Of the total 7343 recipients, 4458 (60.7%) recipients received a kidney from a White donor, 1009 (13.7%) from a Black donor, 1594 (21.7%) from Hispanic donor, and 169 (4.1%) from an Asian donor; 4089 (55.7%) were race-matched. No donor races were significantly associated with transplant outcomes (all P > 0.05). Race-matched status was not associated with graft failure (hazard ratio, 1.03; 95% confidence interval [CI] = 0.89-1.2; P = 0.68), mortality (hazard ratio, 1.1; 95% CI, 0.79-1.53; P = 0.56), acute rejection at 1 y (odds ratio, 0.94; 95% CI, 0.77-1.15; P = 0.53), or delayed graft function (odds ratio, 1.02; 95% CI, 0.80-1.29; P = 0.91). Conclusions: Neither donor race nor race-matched status is associated with better transplant outcomes. Further studies are necessary to confirm the impact of donor race and race-matching more fully on pediatric kidney transplant outcomes.
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Cardiac arrest (CA) produces global ischemia/reperfusion injury resulting in substantial multiorgan damage. There are limited efficacious therapies to save lives despite CA being such a lethal disease process. The small population of surviving patients suffer extensive brain damage that results in substantial morbidity. Mitochondrial dysfunction in most organs after CA has been implicated as a major source of injury. Metformin, a first-line treatment for diabetes, has shown promising results in the treatment for other diseases and is known to interact with the mitochondria. For the treatment of CA, prior studies have utilized metformin in a preconditioning manner such that animals are given metformin well before undergoing CA. As the timing of CA is quite difficult to predict, the present study, in a clinically relevant manner, sought to evaluate the therapeutic benefits of metformin administration immediately after resuscitation using a 10 min asphxyial-CA rat model. This is the first study to show that metformin treatment post-CA (a) improves 72 h survival and neurologic function, (b) protects mitochondrial function with a reduction in apoptotic brain injury without activating AMPK, and (c) potentiates earlier normalization of brain electrophysiologic activity. Overall, as an effective and safe drug, metformin has the potential to be an easily translatable intervention for improving survival and preventing brain damage after CA.
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Lesões Encefálicas , Parada Cardíaca , Metformina , Animais , Modelos Animais de Doenças , Eletroencefalografia , Parada Cardíaca/tratamento farmacológico , Humanos , Metformina/farmacologia , Metformina/uso terapêutico , Mitocôndrias , Neuroproteção , RatosRESUMO
Background: Current allocation mechanisms for liver transplantation (LT) overemphasize emergency, leading to poorer longtime outcomes. The utility was introduced to recognized outcomes in allocation. Recently, Molinari proposed a predictive outcome model based on recipient data. Aims: The aims of this study were to validate this model and to combine it with the utility to emphasize outcome in allocation. Methods: We retrospectively analyzed 734 patients who were transplanted between January 2010 and December 2019. Points were assigned as in Molinari's model and the score sum was correlated with observed 90-day mortality. The utility was calculated as the product of 1-year survival times 3-month mortality on the waiting list. The weighting of different compounds was introduced, and utility curves were calculated. Model for End-Stage Liver Disease (MELD) scores according to maximal utility were determined. Results: In total, 120 patients (16.3%) had died within 90 days after LT. Higher MELD score, obesity, and hemodialysis prior to LT were confirmed risk factors. Overall survival was 83.8 and 77.4% after 90 days and 12 months, respectively. General utility culminated at MELD scores >35 in the overall population. Emphasizing the outcome shifted the maximal utility to lower MELD scores depending on Molinari scores. Conclusions: Emphasizing outcome, at least in certain recipient risk categories, might improve the longtime outcomes and might be integrated into allocation models.
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BACKGROUND: Literature supports equivalent kidney transplant outcomes in adults with systemic lupus erythematosus (SLE) compared with those without SLE. However, there are conflicting and scant data on kidney transplant outcomes, as well as controversy over optimal timing of transplantation, in children and adolescents with SLE. METHODS: Analysis included kidney-only transplant recipients aged 2-21 years from 2000 to 2017 enrolled in the Organ Procurement and Transplant Network (OPTN). The relationship between diagnosis (SLE n = 457, non-SLE glomerular disease n = 4492, and non-SLE non-glomerular disease n = 5605) and transplant outcomes was evaluated. The association between dialysis time and outcomes was analyzed in the SLE group only. RESULTS: In adjusted models, SLE had higher mortality compared with non-SLE glomerular recipients (HR 1.24 CI 1.07-1.44) and non-glomerular recipients (HR 1.42 CI 1.20-1.70). SLE was associated with higher graft failure compared with non-SLE glomerular (HR 1.42 CI 1.20-1.69) and non-glomerular disease (HR 1.67 CI 1.22-2.28). SLE had a higher risk of acute rejection at 1 year compared with non-glomerular disease (HR 1.39 CI 1.03-1.88). There was a decreased risk of delayed graft function compared with non-SLE glomerular disease (HR 0.54, CI 0.36-0.82). There were no significant associations between dialysis time and transplant outcomes in the SLE group. CONCLUSION: SLE in children and adolescents is associated with worse patient and graft survival compared with non-SLE diagnoses. Outcomes in children and adolescents with SLE are not associated with dialysis time. Further studies are needed to assess implications of potential earlier transplantation and shorter time on dialysis prior to transplantation.
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Falência Renal Crônica/cirurgia , Transplante de Rim , Lúpus Eritematoso Sistêmico/complicações , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Bases de Dados Factuais , Função Retardada do Enxerto/epidemiologia , Função Retardada do Enxerto/etiologia , Feminino , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Falência Renal Crônica/etiologia , Falência Renal Crônica/mortalidade , Modelos Logísticos , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
The development of breast cancer depends on several risk factors, including environmental, lifestyle and genetic factors. Despite the evolution of DNA sequencing techniques and biomarker detection, the epidemiology and mechanisms of various breast cancer susceptibility genes have not been elucidated yet. Dysregulation of the DNA damage response causes genomic instability and increases the rate of mutagenesis and the risk of carcinogenesis. The Fanconi Anemia (FA) pathway is an important component of the DNA damage response and plays a critical role in the repair of DNA interstrand crosslinks and genomic stability. The FA pathway involves 22 recognized genes and specific mutations have been identified as the underlying defect in the majority of FA patients. A thorough understanding of the function and epidemiology of these genes in breast cancer is critical for the development and implementation of individualized therapies that target unique tumor profiles. Targeted therapies (PARP inhibitors) exploiting the FA pathway gene defects have been developed and have shown promising results. This narrative review summarizes the current literature on the involvement of FA genes in sporadic and familial breast cancer with a focus on clinical data derived from large cohorts.
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Neoplasias da Mama/metabolismo , Instabilidade Cromossômica , Proteínas de Grupos de Complementação da Anemia de Fanconi/metabolismo , Anemia de Fanconi/metabolismo , Dano ao DNA , Feminino , Instabilidade Genômica , Humanos , MutaçãoRESUMO
In this case report we describe a novel and successful revascularization approach in instances of allograft and distal limb ischemia after kidney transplantation. Stenosis proximal to transplant renal artery anastomoses is a complication leading to allograft dysfunction and/or loss. We present a femorofemoral bypass graft with ringed polytetrafluoroethylene (PTFE). In this occasion, revascularization was achieved by a backflow mechanism. The approach described achieved its goal of revascularizing the allograft as well as the distal extremity, with both short- and long-term successful outcomes. Benefits of this approach when compared with re-implantation or procedures directly involving the transplant renal artery include minimization of ischemic time, no need to repair the stenosis, anastomoses with vessels of greater diameter, no need to perfuse the kidney, no need to take down the renal artery anastomosis, no need to dissect the transplanted kidney, and no further lower extremity ischemia. This approach does not require any proximal temporary inflow occlusion (as seen with stent placement) or clamping of the arterial inflow to the kidney. This procedure was completed without having to infuse any preservation fluid into the kidney.
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BACKGROUND: Despite the benefits of extracorporeal cardiopulmonary resuscitation (ECPR) in cohorts of selected patients with cardiac arrest (CA), extracorporeal membrane oxygenation (ECMO) includes an artificial oxygenation membrane and circuits that contact the circulating blood and induce excessive oxidative stress and inflammatory responses, resulting in coagulopathy and endothelial cell damage. There is currently no pharmacological treatment that has been proven to improve outcomes after CA/ECPR. We aimed to test the hypothesis that administration of hydrogen gas (H2) combined with ECPR could improve outcomes after CA/ECPR in rats. METHODS: Rats were subjected to 20 min of asphyxial CA and were resuscitated by ECPR. Mechanical ventilation (MV) was initiated at the beginning of ECPR. Animals were randomly assigned to the placebo or H2 gas treatment groups. The supplement gas was administered with O2 through the ECMO membrane and MV. Survival time, electroencephalography (EEG), brain functional status, and brain tissue oxygenation were measured. Changes in the plasma levels of syndecan-1 (a marker of endothelial damage), multiple cytokines, chemokines, and metabolites were also evaluated. RESULTS: The survival rate at 4 h was 77.8% (7 out of 9) in the H2 group and 22.2% (2 out of 9) in the placebo group. The Kaplan-Meier analysis showed that H2 significantly improved the 4 h-survival endpoint (log-rank P = 0.025 vs. placebo). All animals treated with H2 regained EEG activity, whereas no recovery was observed in animals treated with placebo. H2 therapy markedly improved intra-resuscitation brain tissue oxygenation and prevented an increase in central venous pressure after ECPR. H2 attenuated an increase in syndecan-1 levels and enhanced an increase in interleukin-10, vascular endothelial growth factor, and leptin levels after ECPR. Metabolomics analysis identified significant changes at 2 h after CA/ECPR between the two groups, particularly in D-glutamine and D-glutamate metabolism. CONCLUSIONS: H2 therapy improved mortality in highly lethal CA rats rescued by ECPR and helped recover brain electrical activity. The underlying mechanism might be linked to protective effects against endothelial damage. Further studies are warranted to elucidate the mechanisms responsible for the beneficial effects of H2 on ischemia-reperfusion injury in critically ill patients who require ECMO support.