RESUMO
BACKGROUND: Atrioventricular block (AVB) secondary to transient causes can recover with its correction. However, studies assessing predictors of recovery and long-term recurrence are lacking. METHODS: Patients with advanced or complete AVB who had a reversible cause admitted in a single expert center were retrospectively studied. Patients with AVB secondary to acute coronary syndromes were excluded from analysis. RESULTS: In a population of 162 patients, the main factors associated with recovery of rhythm without a permanent pacemaker (PPM) implantation were the presence of chronic kidney disease (CKD) on dialysis (OR 7.6; CI 95% 1.2-47.5 (p = .03)); greater serum potassium levels (OR 2.3; CI 95% 1.28-4.0 (p < .01)), higher dosage of bradycardic drugs (OR 2.2; CI 95% 1.13-4.4 (p = .02)), the association between different bradycardic drugs (OR 9.0; CI 95% 2.02-40.3 (p < .01)) and between drug therapy and hyperkaliemia (OR 5.2; CI 95% 1.8-15.1 (p < .01)). There was an overall high burden of conductions abnormalities which did not correlate with recovery of rhythm (OR 0.5; CI 95% 0.19-1.5 (p = .23)). In 29 patients (17.9%) there was a correction of the AVB. During a maximum follow-up of 130 months, 24 patients (82.8%) had a recurrence which warranted a PPM. In the overall cohort only five patients (3%) had sustained recovery of rhythm. CONCLUSIONS: Recovery of AVB was mainly observed with higher doses of drug therapy, higher serum potassium levels or a combination of factors and regardless of baseline conduction abnormalities. The high rate of recurrence during follow-up warrants a close follow-up or PPM implantation at index admission.
Assuntos
Bloqueio Atrioventricular , Marca-Passo Artificial , Humanos , Estudos Retrospectivos , Fatores de Risco , Causalidade , Doença do Sistema de Condução Cardíaco/complicações , Potássio , Marca-Passo Artificial/efeitos adversosRESUMO
OBJECTIVE: To evaluate the feasibility and functional outcomes in porcine models of a novel robotic surgical technique for the treatment of complex ureteral injuries and strictures. MATERIALS AND METHODS: Six pigs underwent robotic ureteral reconstruction using a long tabularized peritoneal flap and followed for 6-9 weeks after the surgery. Ureteral flap vascularity, intra-renal pressure, patency of the conduct, endoscopic aspect of the flap, renal function and histopathology were evaluated. RESULTS: All animals successfully underwent ureteral reconstruction using a tubularized peritoneal flap. Median operative time was 223 min (162-360). Flap tubularization suture took 31 min (19-47), and proximal anastomosis took 20 min (15-38). Bladder mobilization with psoas hitch and distal anastomosis took 9 min (7-12) and 23 min (13-46), respectively. On follow-up, significant shrinkage of the ureteral flap in both length and width was observed. Antegrade pyelograms confirmed dilation and tortuosity of the proximal ureter, dilation of the renal pelvis, and major and minor calyxes without any definitive strictures. Microscopically, focal urothelial lining was seen in the neoureter. Creatinine level was significantly higher at the end of the follow-up period (p = 0.003). CONCLUSIONS: Robot-assisted ureteral reconstruction using a tubularized peritoneum flap is technically feasible and reproducible. The flap sustained abundant vascular supply after different intervals of follow-up and the peritoneal mesenchymal cells differentiated into urothelium and myofibroblasts. Further studies are needed to address the issue of functional obstruction to improve long-term renal function outcomes.
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Peritônio/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Retalhos Cirúrgicos , Ureter/cirurgia , Doenças Ureterais/cirurgia , Procedimentos Cirúrgicos Urológicos/métodos , Animais , Diferenciação Celular , Constrição Patológica/cirurgia , Estudos de Viabilidade , Pelve Renal , Masculino , Células-Tronco Mesenquimais , Modelos Animais , Miofibroblastos , Procedimentos Cirúrgicos Robóticos/métodos , Retalhos Cirúrgicos/irrigação sanguínea , Sus scrofa , Suínos , Ureter/lesões , UrotélioRESUMO
OBJECTIVE: To evaluate contemporary international trends in the implementation of minimally invasive adrenalectomy and to assess contemporary outcomes of different minimally invasive techniques performed at urologic centers worldwide. METHODS: A retrospective multinational multicenter study of patients who underwent minimally invasive adrenalectomy from 2008 to 2013 at 14 urology institutions worldwide was included in the analysis. Cases were categorized based on the minimally invasive adrenalectomy technique: conventional laparoscopy (CL), robot-assisted laparoscopy (RAL), laparoendoscopic single-site surgery (LESS), and mini-laparoscopy (ML). The rates of the four treatment modalities were determined according to the year of surgery, and a regression analysis was performed for trends in all surgical modalities. RESULTS: Overall, a total of 737 adrenalectomies were performed across participating institutions and included in this analysis: 337 CL (46 % of cases), 57 ML (8 %), 263 LESS (36 %), and 80 RA (11 %). Overall, 204 (28 %) operations were performed with a retroperitoneal approach. The overall number of adrenalectomies increased from 2008 to 2013 (p = 0.05). A transperitoneal approach was preferred in all but the ML group (p < 0.001). European centers mostly adopted CL and ML techniques, whereas those from Asia and South America reported the highest rate in LESS procedures, and RAL was adopted to larger extent in the USA. LESS had the fastest increase in utilization at 6 %/year. The rate of RAL procedures increased at slower rates (2.2 %/year), similar to ML (1.7 %/year). Limitations of this study are the retrospective design and the lack of a cost analysis. CONCLUSIONS: Several minimally invasive surgical techniques for the management of adrenal masses are successfully implemented in urology institutions worldwide. CL and LESS seem to represent the most commonly adopted techniques, whereas ML and RAL are growing at a slower rate. All the MIS techniques can be safely and effectively performed for a variety of adrenal disease.
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Doenças das Glândulas Suprarrenais/cirurgia , Adrenalectomia/métodos , Cooperação Internacional , Laparoscopia/métodos , Urologia/tendências , Adrenalectomia/tendências , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Robótica/métodos , Robótica/tendências , Fatores de Tempo , Resultado do TratamentoRESUMO
Acute lymphoblastic leukemia (ALL) is currently treated with an intense regimen of chemotherapy yielding cure rates near 85%. However, alterations to treatment strategies using available drugs are unlikely to provide significant improvement in survival or decrease therapy-associated toxicities. Here, we report ectopic expression of the Mer receptor tyrosine kinase in pre-B-cell ALL (B-ALL) cell lines and pediatric patient samples. Inhibition of Mer in B-ALL cell lines decreased activation of AKT and MAPKs and led to transcriptional changes, including decreased expression of antiapoptotic PRKCB gene and increase in proapoptotic BAX and BBC3 genes. Further, Mer inhibition promoted chemosensitization, decreased colony-forming potential in clonogenic assays, and delayed disease onset in a mouse xenograft model of leukemia. Our results identify Mer as a potential therapeutic target in B-ALL and suggest that inhibitors of Mer may potentiate lymphoblast killing when used in combination with chemotherapy. This strategy could reduce minimal residual disease and/or allow for chemotherapy dose reduction, thereby leading to improved event-free survival and reduced therapy-associated toxicity for patients with B-ALL. Additionally, Mer is aberrantly expressed in numerous other malignancies suggesting that this approach may have broad applications.
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Terapia de Alvo Molecular , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Animais , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , RNA Interferente Pequeno/farmacologia , RNA Interferente Pequeno/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto , c-Mer Tirosina QuinaseRESUMO
OBJECTIVE: To objectively assess ipsilateral renal function (IRF) preservation and factors influencing it after robot-assisted partial nephrectomy (RAPN). PATIENTS AND METHODS: Our database was queried to identify patients who had undergone RAPN from 2007 to 2013 and had complete pre- and postoperative mercapto-acetyltriglycine (MAG3) renal scan assessment. The estimated glomerular filtration rate (eGFR) for the operated kidney was calculated by multiplying the percentage of contribution from the renal scan by the total eGFR. IRF preservation was defined as a ratio of the postoperative eGFR for the operated kidney to the preoperative eGFR for the operated kidney. The percentage of total eGFR preservation was calculated in the same manner (postoperative eGFR/preoperative eGFR × 100). The amount of healthy rim of renal parenchyma removed was assessed by deducting the volume of tumour from the volume of the PN specimen assessed on pathology. Multivariable linear regression was used for analysis. RESULTS: In all, 99 patients were included in the analysis. The overall median (interquartile range) total eGFR preservation and IRF preservation for the operated kidney was 83.83 (75.2-94.1)% and 72 (60.3-81)%, respectively (P < 0.01). On multivariable analysis, volume of healthy rim of renal parenchyma removed, warm ischaemia time (WIT) > 30 min, body mass index (BMI) and operated kidney preoperative eGFR were predictive of IRF preservation. CONCLUSIONS: Using total eGFR tends to overestimate the degree of renal function preservation after RAPN. This is particularly relevant when studying factors affecting functional outcomes after nephron-sparing surgery. IRF may be a more precise assessment method in this setting. Operated kidney baseline renal function, BMI, WIT >30 min, and amount of resected healthy renal parenchyma represent the factors with a significant impact on the IRF preservation. RAPN provides significant preservation of renal function as shown by objective assessment criteria.
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Rim/fisiologia , Nefrectomia/métodos , Procedimentos Cirúrgicos Robóticos , Feminino , Taxa de Filtração Glomerular , Humanos , Rim/anatomia & histologia , Testes de Função Renal/métodos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Período Pós-Operatório , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Tecnécio Tc 99m MertiatidaRESUMO
The aim of this study was to provide a systematic review and meta-analysis of reports comparing laparoendoscopic single-site (LESS) living-donor nephrectomy (LDN) vs standard laparoscopic LDN (LLDN). A systematic review of the literature was performed in September 2013 using PubMed, Scopus, Ovid and The Cochrane library databases. Article selection proceeded according to the search strategy based on Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria. Weighted mean differences (WMDs) were used to measure continuous variables and odds ratios (ORs) to measure categorical ones. Nine publications meeting eligibility criteria were identified, including 461 LESS LDN and 1006 LLDN cases. There were more left-side cases in the LESS LDN group (96.5% vs 88.6%, P < 0.001). Meta-analysis of extractable data showed that LLDN had a shorter operative time (WMD 15.06 min, 95% confidence interval [CI] 4.9-25.1; P = 0.003), without a significant difference in warm ischaemia time (WMD 0.41 min, 95% CI -0.02 to 0.84; P = 0.06). Estimated blood loss was lower for LESS LDN (WMD -22.09 mL, 95% CI -29.5 to -14.6; P < 0.001); however, this difference was not clinically significant. There was a greater likelihood of conversion for LESS LDN (OR 13.21, 95% CI 4.65-37.53; P < 0.001). Hospital stay was similar (WMD -0.11 days, 95% CI -0.33 to 0.12; P = 0.35), as well as the visual analogue pain score at discharge (WMD -0.31, 95% CI -0.96 to 0.35; P = 0.36), but the analgesic requirement was lower for LESS LDN (WMD -2.58 mg, 95% CI -5.01 to -0.15; P = 0.04). Moreover, there was no difference in the postoperative complication rate (OR 1.00, 95% CI 0.65-1.54; P = 0.99). Renal function of the recipient, as based on creatinine levels at 1 month, showed similar outcomes between groups (WMD 0.10 mg/dL, -0.09 to 0.29; P = 0.29). In conclusion, LESS LDN represents an emerging option for living kidney donation. This procedure offers comparable surgical and early functional outcomes to the conventional LLDN, with a lower analgesic requirement. However, it is more technically challenging than LLDN, as shown by a greater likelihood of conversion. The role of LESS LDN remains to be defined.
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Falência Renal Crônica/cirurgia , Transplante de Rim , Laparoscopia , Doadores Vivos , Nefrectomia , Endoscopia , Humanos , Falência Renal Crônica/mortalidade , Transplante de Rim/efeitos adversos , Transplante de Rim/métodos , Transplante de Rim/mortalidade , Laparoscopia/métodos , Laparoscopia/mortalidade , Nefrectomia/efeitos adversos , Nefrectomia/métodos , Nefrectomia/mortalidade , Duração da Cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Isquemia QuenteRESUMO
INTRODUCTION: Partial nephrectomy is the standard of care for localized renal tumors. However, bleeding and warm ischemia time are still controversial when laparoscopic surgeries are carried out. Herein, we aim to compare the outcomes from laparoscopic partial nephrectomy with and without the use of biological glue with purified bovine albumin and glutaraldehyde (BioGlue ®). MATERIALS AND METHODS: Twenty-four kidneys of 12 pigs were used in this study. A pre-determined lower pole segment was resected (3 cm x 1 cm) and one of two different hemostatic techniques was performed. In one kidney, hemostatic â³ U suture â³ (poliglecaprone 3.0) was performed and in the contra-lateral kidney, only the biological glue was applied. Data recorded was comprised of warm ischemia time (seconds) and estimated blood loss (mL) for each procedure. In cases of bleeding after glue administration, a complementary suture was done. RESULTS: Mean warm ischemia time was 492.9 ± 113.1 (351-665) seconds and 746 ± 185.3 (409-1125) seconds for biological glue and suture groups, respectively. There was a positive significant difference in terms of warm ischemia favoring the biological glue group over the suture group (p<0.001). Mean blood loss was 39.4 (0-115) mL for the biological glue group and 39.1 (5-120) mL for the suture group (p=0.62). CONCLUSION: Biological glue is an important tool for laparoscopic partial nephrectomies. It is effective for hemostatic control in selected cases, and it can be used in combination with the traditional suture techniques.
Assuntos
Glutaral/uso terapêutico , Rim/cirurgia , Laparoscopia/métodos , Nefrectomia/métodos , Proteínas/uso terapêutico , Técnicas de Sutura , Animais , Perda Sanguínea Cirúrgica , Rim/irrigação sanguínea , Neoplasias Renais/cirurgia , Ilustração Médica , Modelos Animais , Valores de Referência , Reprodutibilidade dos Testes , Albumina Sérica/uso terapêutico , Suínos , Fatores de Tempo , Resultado do Tratamento , Isquemia Quente/métodosRESUMO
PURPOSE: After CMS introduced the concept of the Hospital Readmissions Reduction Program, hospitals and health care centers became financially penalized for exceeding specific readmission rates. MATERIALS AND METHODS: We retrospectively reviewed our institutional review board approved database of patients undergoing robotic partial nephrectomy at our institution and included in our analysis patients who were readmitted to any hospital as an inpatient stay within 30 days from discharge home after robotic partial nephrectomy. RESULTS: From March 2006 to March 2013 a total of 627 patients underwent robotic partial nephrectomy at our center and 28 (4.46%) were readmitted within 30 days of surgery. Postoperative bleeding was responsible for 8 (28.5%) readmissions. Pulmonary embolism was reported in 3 cases and retroperitoneal abscess was diagnosed in 2. Urinary leak requiring surgical intervention developed in 2 patients, pneumonia was diagnosed in 2 and 2 patients were readmitted for chest pain. Overall 9 (32.1%) patients presented with major complications requiring intervention. On multivariable analysis Charlson comorbidity index score was the only factor significantly associated with a higher 30-day readmission rate (p = 0.03). If the Charlson score was 5 or greater the chance of hospital readmission would be 2.7 times higher. CONCLUSIONS: Increased comorbidity, specifically a Charlson score of 5 or greater, was the only significant predictor of a higher incidence of 30-day readmission. This information can be useful in counseling patients regarding robotic partial nephrectomy and in determining baseline rates if CMS expands the number of conditions they evaluate for excess 30-day readmissions.
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Medicare , Nefrectomia/métodos , Readmissão do Paciente/estatística & dados numéricos , Robótica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Estados UnidosRESUMO
INTRODUCTION: A duplicated renal collecting system is a relatively common congenital anomaly rarely presenting in adults. AIM: In this video we demonstrate our step-by-step technique of Robotic heminephrectomy in a patient with non-functioning upper pole moiety. MATERIALS AND METHODS: Following cystoscopy and ureteral catheter insertion the patient was placed in 60° modified flank position with the ipsilateral arm positioned at the side of the patient. A straight-line, three arm robotic port configuration was employed. The robot was docked at a 90-degree angle, perpendicular to the patient. Following mobilization the colon and identifying both ureters of the duplicated system, the ureters were followed cephalically toward, hilar vessels where the hilar anatomy was identified. The nonfunctioning pole vasculature was ligated using hem-o-lok clips. The ureter was sharply divided and the proximal ureteral stump was passed posterior the renal hilum. Ureteral stump was used as for retraction and heminephrectomy is completed along the line demarcating the upper and lower pole moieties. Renorrhaphy was performed using 0-Vicryl suture with a CT-1 needle. The nonfunctioning pole ureter was then dissected caudally toward the bladder hiatus, ligated using clips, and transected. RESULTS: The operating time was 240 minutes and blood loss was 100 cc. There was no complication post-operatively. CONCLUSIONS: Wrist articulation and degree of freedom offered by robotic platform facilitates successful performance of minimally invasive heminephrectomy in the setting of an atrophic and symptomatic renal segment.
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Túbulos Renais Coletores/anormalidades , Túbulos Renais Coletores/cirurgia , Nefrectomia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Ureter/cirurgia , Feminino , Humanos , Duração da Cirurgia , Reprodutibilidade dos Testes , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: To investigate risk factors for urine leak in patients undergoing minimally invasive partial nephrectomy (MIPN) and to determine the role of intraoperative ureteral catheterization in preventing this postoperative complication. MATERIALS AND METHODS: MIPN procedures done from September 1999 to July 2012 at our Center were reviewed from our IRB-approved database. Patient and tumor characteristics, operative techniques and outcomes were analyzed. Patients with evidence of urine leak were identified. Outcomes were compared between patients with preoperative ureteral catheterization (C-group) and those without (NC-group). Univariable and multivariable analyses were performed to identify factors predicting postoperative urine leak. RESULTS: A total of 1,019 cases were included (452 robotic partial nephrectomy cases and 567 laparoscopic partial nephrectomy cases). Five hundred twenty eight patients (51.8%) were in the C-group, whereas 491 of them (48.2%) in the NC-group. Urine leak occurred in 31(3%) cases, 4.6% in the C-group and 1.4% in the NC-group (p<0.001). Tumors in NC-group had significantly higher RENAL score, shorter operative and warm ischemic times. On multivariable analysis, tumor proximity to collecting system (OR=9.2; p<0.01), surgeon's early operative experience (OR=7.8; p<0.01) and preoperative moderate to severe CKD (OR=3.1; p<0.01) significantly increased the odds of the occurrence of a postoperative urine leak. CONCLUSION: Clinically significant urine leak after MIPN in a high volume institution setting is uncommon. This event is more likely to occur in cases of renal masses that are close to the collecting system, in patients with preoperative CKD and when operating surgeon is still in the learning curve for the procedure. Our findings suggest that routine intraoperative ureteral catheterization during MIPN does not reduce the probability of postoperative urine leak. In addition, it adds to the overall operative time.
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Nefrectomia/efeitos adversos , Cateterismo Urinário/métodos , Incontinência Urinária/etiologia , Incontinência Urinária/prevenção & controle , Idoso , Feminino , Taxa de Filtração Glomerular , Humanos , Cuidados Intraoperatórios , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Análise Multivariada , Nefrectomia/métodos , Duração da Cirurgia , Insuficiência Renal Crônica/cirurgia , Reprodutibilidade dos Testes , Fatores de Risco , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Cryoballoon ablation (CBA) for pulmonary vein isolation (PVI) has been growing as an alternative technique, not only in patients with paroxysmal atrial fibrillation (PAF) but also in persistent atrial fibrillation (AF). Cryoballoon ablation has demonstrated encouraging acute and mid-term results. However, data on long-term follow-up of CB-based PVI are scarce. OBJECTIVE: We sought to examine efficacy, safety, and long-term outcomes of CBA in PAF and persistent AF in four Portuguese centers. METHODS: All patients that were treated with the cryoballoon catheter according to routine practices with a second-generation 28-mm CB in four centers were included. This was a retrospective, non-randomized analysis. Patients were followed-up for >12 months and freedom from atrial arrhythmias (AA) was evaluated at the end of follow-up. RESULTS: Four hundred and six patients (57.7±12.4 years, 66% men) participated. AF was paroxysmal in 326 patients (80.2%) and persistent in 80 (19.7%). The mean procedure time duration was 107.7±50.9 min, and the fluoroscopy time was 19.5±9.7 min. Procedural/periprocedural complications occurred in 30 cases (7.3%), being transient phrenic nerve palsy the most frequent incident (2 out of 3 complications). Anatomic variations of the PV were present in 16.1% of cases. At a mean follow-up of 22.0±15.0 months, 310 patients (76.3%) remained in stable sinus rhythm, with at least one AF episode recurrence documented in 98 cases (24.1%). The recurrence rate was 20.5% in the PAF group and 37.8% in the persistent AF group. CONCLUSION: In this multicenter experience, a single CBA procedure resulted in 75.9% freedom from AF at a 22-month follow-up. This technique was demonstrated to be a safe and effective option in experienced centers for the treatment of PAF and PersAF.
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Fibrilação Atrial , Ablação por Cateter , Criocirurgia , Veias Pulmonares , Masculino , Humanos , Feminino , Fibrilação Atrial/complicações , Portugal , Resultado do Tratamento , Estudos Retrospectivos , Ablação por Cateter/métodos , Veias Pulmonares/cirurgia , RecidivaRESUMO
Acute lymphoblastic leukemia (ALL) is currently treated with an intense regimen of chemotherapy yielding cure rates near 80%. However, additional changes using available drugs are unlikely to provide significant improvement in survival. New therapies are warranted given the risk of severe therapy-associated toxicities including infertility, organ damage, and secondary malignancy. Here, we report ectopic expression of the receptor tyrosine kinase Mer in pediatric B-cell ALL. Inhibition of Mer prevented Erk 1/2 activation, increased the sensitivity of B-ALL cells to cytotoxic agents in vitro by promoting apoptosis, and delayed disease onset in a mouse model of leukemia. In addition, we discovered cross-talk between the Mer and mammalian target of rapamycin (mTOR) signaling pathways. Our results identify Mer as a novel therapeutic target in ALL and suggest that inhibitors of Mer will interact synergistically with currently used therapies. This strategy may allow for dose reduction resulting in decreased toxicity and increased survival rates. Mer is aberrantly expressed in numerous other malignancies suggesting that this approach may have broad applications.
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Sistemas de Liberação de Medicamentos , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Proteínas Proto-Oncogênicas/fisiologia , Receptores Proteína Tirosina Quinases/fisiologia , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Sobrevivência Celular/genética , Criança , Sistemas de Liberação de Medicamentos/métodos , Regulação Leucêmica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Proteínas Proto-Oncogênicas/genética , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/farmacologia , RNA Interferente Pequeno/uso terapêutico , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Receptores Proteína Tirosina Quinases/genética , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto , c-Mer Tirosina QuinaseRESUMO
Background. Wolff-Parkinson-White syndrome is an uncommon cardiac disorder characterized by the presence of one or more accessory pathways that predispose patients to frequent episodes of arrhythmias. The prognosis is usually good, but there is a lifetime risk of malignant arrhythmias and sudden cardiac death. Case Summary. A 25-year-old male presented a witnessed out-of-hospital cardiac arrest with ventricular fibrillation rhythm. Due to rapid initiation of prehospital advanced life support, return of spontaneous circulation was observed. During the transport to the hospital, an irregular wide complex tachycardia suggestive of preexcited atrial fibrillation with haemodynamic instability was also observed and a synchronized shock was applied. Baseline 12-lead electrocardiogram was compatible with sinus rhythm and ventricular preexcitation pattern. After clinical stabilization, an electrophysiological study was performed confirming the presence of a left anterolateral accessory pathway with a short antegrade effective refractory period. Successful radiofrequency catheter ablation was achieved. Discussion. The reported clinical case recalls fundamental features of the Wolff-Parkinson-White syndrome and outlines the increasing evidence and importance of the invasive risk stratification and even catheter ablation in asymptomatic patients who suffer from this uncommon disease that may have a dramatic and fatal initial clinical manifestation.
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Procedimentos Cirúrgicos Minimamente Invasivos , Nefrectomia , Complicações Pós-Operatórias/epidemiologia , Isquemia Quente/estatística & dados numéricos , Humanos , Neoplasias Renais/cirurgia , Metanálise como Assunto , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Nefrectomia/efeitos adversos , Nefrectomia/métodos , Resultado do TratamentoRESUMO
Eukaryotic chromosomal replication is a complicated process with many origins firing at different efficiencies and times during S phase. Prereplication complexes are assembled on all origins in G(1) phase, and yet only a subset of complexes is activated during S phase by DDK (for Dbf4-dependent kinase) (Cdc7-Dbf4). The yeast mcm5-bob1 (P83L) mutation bypasses DDK but results in reduced intrinsic firing efficiency at 11 endogenous origins and at origins located on minichromosomes. Origin efficiency may result from Mcm5 protein assuming an altered conformation, as predicted from the atomic structure of an archaeal MCM (for minichromosome maintenance) homologue. Similarly, an intragenic mutation in a residue predicted to interact with P83L suppresses the mcm5-bob1 bypass phenotype. We propose DDK phosphorylation of the MCM complex normally results in a single, highly active conformation of Mcm5, whereas the mcm5-bob1 mutation produces a number of conformations, only one of which is permissive for origin activation. Random adoption of these alternate states by the mcm5-bob1 protein can explain both how origin firing occurs independently of DDK and why origin efficiency is reduced. Because similar mutations in mcm2 and mcm4 cannot bypass DDK, Mcm5 protein may be a unique Mcm protein that is the final target of DDK regulation.
Assuntos
Proteínas de Ciclo Celular/química , Proteínas de Ciclo Celular/metabolismo , Replicação do DNA , Proteínas Serina-Treonina Quinases/metabolismo , Origem de Replicação , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas Cromossômicas não Histona , Cromossomos Fúngicos/metabolismo , DNA Fúngico/metabolismo , Proteínas de Ligação a DNA/genética , Eletroforese em Gel Bidimensional , Proteínas Fúngicas/genética , Componente 4 do Complexo de Manutenção de Minicromossomo , Mutação/genética , Plasmídeos , Estrutura Terciária de Proteína , Saccharomyces cerevisiae/citologia , Proteínas de Saccharomyces cerevisiae/genética , Relação Estrutura-AtividadeRESUMO
A 70-year-old man developed drug refractory acute pulmonary oedema secondary to acute severe mitral regurgitation (MR) immediately after implantation of a dual-chamber pacemaker for complete heart block. Clinical improvement occurred after allowing the patient to resume his native rhythm. A new lead was positioned within the right ventricular outflow tract (RVOT). The echocardiogram during pacing at RVOT showed minimal MR.
Assuntos
Bloqueio Cardíaco/terapia , Insuficiência da Valva Mitral/etiologia , Marca-Passo Artificial/efeitos adversos , Doença Aguda , Idoso , Ecocardiografia Doppler , Humanos , Masculino , Insuficiência da Valva Mitral/complicações , Insuficiência da Valva Mitral/diagnóstico por imagem , Edema Pulmonar/etiologiaRESUMO
A special metric of interest about Boolean functions is multiplicative complexity (MC): the minimum number of AND gates sufficient to implement a function with a Boolean circuit over the basis {XOR, AND, NOT}. In this paper we study the MC of symmetric Boolean functions, whose output is invariant upon reordering of the input variables. Based on the Hamming weight method from Muller and Preparata (1975), we introduce new techniques that yield circuits with fewer AND gates than upper bounded by Boyar et al. in 2000 and by Boyar and Peralta in 2008. We generate circuits for all such functions with up to 25 variables. As a special focus, we report concrete upper bounds for the MC of elementary symmetric functions ∑ k n and counting functions ∑ k n with up to n = 25 input variables. In particular, this allows us to answer two questions posed in 2008: both the elementary symmetric ∑ 4 8 and the counting ∑ 4 8 functions have MC 6. Furthermore, we show upper bounds for the maximum MC in the class of n-variable symmetric Boolean functions, for each n up to 132.
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The security of encrypted data depends not only on the theoretical properties of cryptographic primitives but also on the robustness of their implementations in software and hardware. Threshold cryptography introduces a computational paradigm that enables higher assurance for such implementations.
RESUMO
We describe a 79-year-old male patient with no significant risk factors for coronary heart disease besides age and gender. He was referred for cardiology consultation because of effort dyspnea. Diagnostic exams including laboratory tests, chest X-ray, ECG and resting echocardiogram showed no abnormalities. He underwent exercise stress echocardiography, which revealed reduced exercise tolerance and a dynamic left ventricular outflow tract obstruction with an intraventricular gradient of over 50 mmHg. No segmental wall motion abnormalities were observed. He was treated with the beta-blocker bisoprolol 5 mg qd, with significant clinical improvement. Two years later exercise stress echocardiography was repeated and better functional capacity was apparent, with no intraventricular gradient during peak exercise. The authors discuss the clinical importance of this unsuspected cause of symptoms in the elderly.