Detection of microcirculatory impairment by transcutaneous oxymetry monitoring during hemodialysis: an observational study.

BACKGROUND: Little is known about the effects of intermittent hemodialysis on microcirculatory perfusion. The aim of this study is to assess the effects of hemodialysis on microvascular perfusion using transcutaneous oxymetry (TCPO2). METHODS: In this observational study, hourly TCPO2 measurements were performed during hemodialysis sessions. Ankle brachial index (ABI) was carried out to classify patients according their vascular condition. RESULTS: 50 patients (mean age 70 ± 8 years old) were enrolled. Mean TCPO2 decreased significantly on average 23.9% between start and finish of hemodialysis. Severe ischemia (TCPO2 < 30 mmHg) and critical ischemia (TCPO2 < 10 mmHg) occurred during dialysis in 47.1% and 15.5% respectively. Critical ischemia occurred only in limbs with ABI < 0.9 (8.3%) or > 1.3 (28%). Patients with critical ischemia experienced a significantly larger decline in mean blood pressure (32.4 ± 26.1 mmHg vs 12.7 ± 10.7 mmHg; P = 0.007) and a more pronounced ultrafiltration (45.55 ± 16.9 ml/kg vs 35.17 ± 18.2 ml/kg; P = 0.04) compared to patients without ischemia. Clinical outcomes (death or vascular procedures) were five times more frequent in patients who had developed critical ischemia (55.7% vs 10.1% P = 0.01). The elevated age of patients, the low basal value of TCPO2, and the occurrence of critical ischemia were more frequently associated with clinical outcome (P = 0.03, P = 0.048, P = 0.01 respectively). CONCLUSIONS: This study demonstrates that hemodialysis induces microcirculatory injury, dependent on blood pressure reduction, peripheral vascular state and ultrafiltration. The occurrence of critical ischemia is associated to pejorative patient outcome and therefore, TCPO2 seems to be useful to avoid potential distal tissue damage during hemodialysis.

Characterization of the patterns of care, access, and direct cost of systemic lupus erythematosus in Brazil: findings from the Macunaíma study.

BACKGROUND: A cost of illness (COI) study aims to evaluate the socioeconomic burden that an illness imposes on society as a whole. This study aimed to describe the resources used, patterns of care, direct cost, and loss of productivity due to systemic lupus erythematosus (SLE) in Brazil. METHODS: This 12-month, cross-sectional, COI study of patients with SLE (ACR 1997 Classification Criteria) collected data using patient interviews (questionnaires) and medical records, covering: SLE profile, resources used, morbidities, quality of life (12-Item Short Form Survey, SF-12), and loss of productivity. Patients were excluded if they were retired or on sick leave for another illness. Direct resources included health-related (consultations, tests, medications, hospitalization) or non-health-related (transportation, home adaptation, expenditure on caregivers) hospital resources.Costs were calculated using the unit value of each resource and the quantity consumed. A gamma regression model explored cost predictors for patients with SLE. RESULTS: Overall, 300 patients with SLE were included (92.3% female,mean [standard deviation (SD)] disease duration 11.8 [7.9] years), of which 100 patients (33.3%) were on SLE-related sick leave and 46 patients (15.3%) had stopped schooling. Mean (SD) travel time from home to a care facility was 4.4 (12.6) hours. Antimalarials were the most commonly used drugs (222 [74.0%]). A negative correlation was observed between SF-12 physical component and SLE Disease Activity Index (- 0.117, p = 0.042), Systemic Lupus International CollaboratingClinics/AmericanCollegeofRheumatology Damage Index (- 0.115, p = 0.046), medications/day for multiple co-morbidities (- 0.272, p < 0.001), SLE-specific drugs/day (- 0.113, p = 0.051), and lost productivity (- 0.570, p < 0.001). For the mental component, a negative correlation was observed with medications/day for multiple co-morbidities (- 0.272, p < 0.001), SLE-specific medications/day (- 0.113, p = 0.051), and missed appointments (- 0.232, p < 0.001). Mean total SLE cost was US$3,123.53/patient/year (median [interquartile range (IQR)] US$1,618.51 [$678.66, $4,601.29]). Main expenditure was medication, with a median (IQR) cost of US$910.62 ($460, $4,033.51). Mycophenolate increased costs by 3.664 times (p < 0.001), and inflammatory monitoring (erythrocyte sedimentation rate or C-reactive protein) reduced expenditure by 0.381 times (p < 0.001). CONCLUSION: These results allowed access to care patterns, the median cost for patients with SLE in Brazil, and the differences across regions driven by biological, social, and behavioral factors. The cost of SLE provides an updated setting to support the decision-making process across the country.

A rare case of visceral arterial stenoses in Williams-Beuren syndrome treated by complex revascularization.

Williams-Beuren syndrome is a rare neurodevelopmental disorder. We present the case of a 27-year-old patient with Williams-Beuren syndrome and a juxtarenal abdominal aorta coarctation. As arterial hypertension (AHT) was not controlled, bilateral renal artery bypasses were performed at the age of 2 years by means of a hepatorenal bypass and a splenorenal bypass. Twenty years later, the patient presented with abdominal pain, diarrhea, and recurrence of AHT, and severe celiac artery and superior mesenteric artery stenoses were discovered. The distal arterial complications of this syndrome are uncommon. After 5 years of medical treatment, aggravation of the patient's symptoms prompted us to consider possible surgical management. The patient was successfully treated using a complex direct and indirect procedure that consisted of a bypass between the celiac aorta and infrarenal aorta, associated with a celiac artery bypass. Instead of endovascular management, this surgical procedure could be considered effective and long lasting for treating this rare cause of renal AHT.

Aortic aneurysm surgery: long-term patency of the reimplanted intercostal arteries.

BACKGROUND: During aortic surgery, the long-term patency of reimplanted intercostal arteries is unknown, limiting the relevance to preserve spinal cord vascularization. METHODS: Between January 2001 and January 2007, 40 patients were operated for either thoracic aortic aneurysm (TAA) or thoracoabdominal aortic aneurysm (TAAA). Twenty cases of aneurysms limited to the proximal descending thoracic aorta were treated using endovascular repair, without preoperative spinal cord artery identification. Twenty patients--seven with extensive TAA, seven with type I TAAA, two with type II TAAA, and four with type III TAAA--underwent open surgery. Before open surgery, preoperative angiography was performed to identify spinal cord vascularization; in one case, the angiography failed to identify it. The segmental artery destined to the spinal cord artery was identified as originating from outside the aneurysm in 7 patients and inside the aneurysm in 12 patients: T6 R (1), T8 L (2), T9 L (3), T10 L (3), T11 L (3), L1 L (1). During the surgery, normothermic and femorofemoral bypass was used for visceral protection. All segmental arteries identified as critical before surgery were reattached in the graft. Twenty-four months later, computed tomography scans were performed to assess the patency of the reattached segmental arteries. RESULTS: Three patients died, including one with paraplegia (T9 L). No other cases of paraplegia were reported. Computed tomography scans were performed in 10 patients. Segmental artery reattachment was patent in nine patients. CONCLUSION: Our experience indicates the long-term patency of reimplanted segmental artery, without any convincing evidence of its utility in preventing neurologic events during TAA and TAAA direct repair.

Intraoperative factors affecting renal outcome after open repair of suprarenal aortic aneurysms.

BACKGROUND: The open repair of suprarenal aortic aneurysm requires supraceliac aortic cross-clamping and separate renal artery reconstruction. The aim of this study was to determine the intraoperative factors responsible for postoperative renal dysfunction. METHODS: Between January 1, 2000 and May 31, 2010, 54 suprarenal aortic aneurysms were repaired at our center (mean age of the patients, 66 ± 8 years). All cases were operated through a left retroperitoneal approach without left renal vein division. Acute kidney injury was defined as a 50% increase of serum creatinine level from the preoperative baseline concentration. Perioperative variables were tested to be correlated with renal dysfunction (Spearman rank). RESULTS: The ischemic time was 28 ± 8 minutes for the mesentery and the right kidney and 63 ± 16 minutes for the left kidney. The total aortic clamping time was 115 ± 27 minutes. The volume of autologous transfusion was 957 ± 479 mL, allogeneic transfusion was 936 ± 473 mL, and colloids and crystalloids was 7,194 ± 2,201 mL. Two patients died. Acute kidney injury occurred in 15 patients, with complete recovery at discharge. The autologous blood transfusion volume (P = 0.009, r = 0.36) and the total aortic clamping time (P = 0.04, r = 0.30) were correlated with renal dysfunction. CONCLUSION: Postoperative renal dysfunction based on the variation in creatinine serum level was transient and requires further investigation using sensitive biomarkers for tubular ischemia.

Syngeneic bone marrow cell therapy prevents intimal proliferation in allogeneic vascular transplantation.

BACKGROUND: Transplant arteriosclerosis is characterized by intraluminal obstructive proliferation occurring in response to immune-mediated arterial wall injury. Cell therapy with vascular progenitor cells have been suggested to repair intimal lesions following endothelial injury. The aim of the current study was to assess the effects of autologous bone marrow cell direct transfer and of Fucan-mobilization bone marrow-derived progenitor cells on intimal thickening in vascular grafts. METHODS: Aortic allografts were performed in Brown Norway (BN) and Lewis (LEW) rats. Cell therapy was performed by injection of two doses of 10 million LEW bone marrow mononuclear cells to recipient LEW following aortic grafting. Fucan, a low molecular weight sulfated polysaccharide (LMWF) was used to mobilize bone marrow-derived progenitor cells. Five groups of 10 rats included: untreated isografts (BN to BN), untreated allografts, and three allografted groups, respectively, treated by fucan therapy, cell therapy, or cell and fucan therapy. Aorta were studied by morphometric analysis at 30 d. RESULTS: In the absence of treatment, intimal thickening was greater in allograft than in isograft groups (299±50 versus 3.5±1.7 µm, P<0.001). Cell therapy alone, fucan therapy alone, and the combined treatment were shown to prevent intimal thickening in allografts (5.1±1.7, 6.1±2.3, 4.1±2.5, versus 299±50 µm respectively, P<0.001). In the three treated groups, the intimal lining was a single layer of endothelial cells expressing CD34 positive, endothelial nitric oxide synthase (eNOS) positive, and Ox3 specific-recipient monoclonal antibody positive. CONCLUSION: These results provide the proof of concept of recipient syngenic bone-marrow cell therapy for the prevention of chronic vasculopathy.

Open repair of extensive thoracoabdominal and thoracic aneurysm: a preliminary single-center experience with femorofemoral distal aortic perfusion with oxygenator and without cerebrospinal fluid drainage.

Thoracoabdominal aortic aneurysms (TAAA) and extensive thoracic descending aortic aneurysms (TDA) are not accessible through standard endovascular treatment. Fenestrated and branched endograft technology was developed rapidly without widespread application. The aim of this study was to review our open repair (OR) experience of TAAA and TDA. A total of 28 patients who underwent elective OR of TAAA or TDA between January 2001 and January 2009 were analyzed retrospectively. The mean age of the patients was 65.5 years (three women). The anatomic locations of the aneurysms were as follows: six in thoracic descending aorta and 22 in thoracoabdominal aorta (14 TAAA I, two TAAA II, six TAAA III). TDA (40 patients) available for ordinary endovascular treatment and TAAA IV (35 patients) were excluded from this study. To focus on spinal cord vascularization, 25 patients were submitted for angiography. Three patients suffering from back pain required quick treatment and were excluded from angiographic investigations. Angiography procedures were contributive in 23 patients (92%). Surgical repairs were driven through left thoraco-phreno-laparotomy, with the adjunct of distal aortic perfusion (femorofemoral bypass) including the use of an oxygenator and sequential aortic cross-clamping. Cerebrospinal fluid drainage was not used in this experience. The 30-day mortality rate was 14.3% (four of 28 patients): one multiorgan failure and three pulmonary sepsis. An immediate postoperative paraplegia occurred, affecting a patient with TDA who was previously submitted for infrarenal aorta replacement, despite angiographic identification and revascularization of intercostal artery destined to spinal artery. The 1-year survival rate was 82.1% (23 of 28 patients). In the preliminary experience of this study, OR of extensive TAAA and TDA with distal aortic perfusion and an oxygenator without use of cerebrospinal fluid drainage was associated with a significant perioperative mortality rate (14.2%), a reasonable rate of paraplegia (3%), and 1-year survival rate of 82.1%.

Characterization of the patterns of care, access, and direct cost of systemic lupus erythematosus in Brazil: findings from the Macunaíma study

Abstract Background A cost of illness (COI) study aims to evaluate the socioeconomic burden that an illness imposes on society as a whole. This study aimed to describe the resources used, patterns of care, direct cost, and loss of productivity due to systemic lupus erythematosus (SLE) in Brazil. Methods This 12-month, cross-sectional, COI study of patients with SLE (ACR 1997 Classification Criteria) collected data using patient interviews (questionnaires) and medical records, covering: SLE profile, resources used, morbidities, quality of life (12-Item Short Form Survey, SF-12), and loss of productivity. Patients were excluded if they were retired or on sick leave for another illness. Direct resources included health-related (consultations, tests, medications, hospitalization) or non-health-related (transportation, home adaptation, expenditure on caregivers) hospital resources. Costs were calculated using the unit value of each resource and the quantity consumed. A gamma regression model explored cost predictors for patients with SLE. Results Overall, 300 patients with SLE were included (92.3% female, mean [standard deviation (SD)] disease duration 11.8 [7.9] years), of which 100 patients (33.3%) were on SLE-related sick leave and 46 patients (15.3%) had stopped schooling. Mean (SD) travel time from home to a care facility was 4.4 (12.6) hours. Antimalarials were the most commonly used drugs (222 [74.0%]). A negative correlation was observed between SF-12 physical component and SLE Disease Activity Index (- 0.117, p = 0.042), Systemic Lupus International CollaboratingClinics/AmericanCollegeofRheumatology Damage Index (- 0.115, p = 0.046), medications/day for multiple co-morbidities (- 0.272, p < 0.001), SLE-specific drugs/day (- 0.113, p = 0.051), and lost productivity (- 0.570, p < 0.001). For the mental component, a negative correlation was observed with medications/day for multiple co-morbidities (- 0.272, p < 0.001), SLE-specific medications/day (- 0.113, p = 0.051), and missed appointments (- 0.232, p < 0.001). Mean total SLE cost was US$3,123.53/patient/year (median [interquartile range (IQR)] US$1,618.51 [$678.66, $4,601.29]). Main expenditure was medication, with a median (IQR) cost of US$910.62 ($460, $4,033.51). Mycophenolate increased costs by 3.664 times (p < 0.001), and inflammatory monitoring (erythrocyte sedimentation rate or C-reactive protein) reduced expenditure by 0.381 times (p < 0.001). Conclusion These results allowed access to care patterns, the median cost for patients with SLE in Brazil, and the differences across regions driven by biological, social, and behavioral factors. The cost of SLE provides an updated setting to support the decision-making process across the country.

Low molecular weight fucoidan prevents neointimal hyperplasia after aortic allografting.

BACKGROUND: Fucoidan, a new low molecular weight sulfated polysaccharide (LMWF), has previously been shown to mobilize bone marrow-derived progenitors cells via stimulation of stromal derived factor (SDF)-1 release. Mobilized progenitor cells have been suggested to repair intimal lesions after immune-mediated endothelial injury and thus prevent intimal proliferation. The aim of this study was to evaluate the effect of LMWF treatment in a rat aortic allograft model of transplant arteriosclerosis (TA). METHODS: Aortic grafts were performed in Brown Norway (BN, donor) and Lewis (Lew, recipient) rats. The recipient rats were treated with LMWF (5 mg/kg/day) and sacrificed at 30 days. To determine the role of SDF-1 in mediating the effects of LMWF, a specific inhibitor of the SDF-1 receptor CXCR4, AMD 3100 (20 microg/kg/day), was used. The grafted segments were evaluated by morphometric (histochemical) analyses. RESULTS: Untreated aortic allografts exhibited severe intimal proliferation, indicative of TA. In contrast, LMWF treatment significantly prevented allograft intimal proliferation as compared with controls (5.7+/-3 vs. 66.2+/-6 microm, P<0.01) and permitted a normalization of the intima/media ratio (0.1+/-0.1 vs. 1.7+/-0.3, P<0.01). Further, LMWF treatment stimulated allograft reendothelialization, as evidenced by strong intimal endothelial nitric oxide synthase antibody and CD31 signals. Unexpectedly, AMD treatment failed to prevent the protective effect of LMWF on intimal thickening and AMD treatment alone was found to reduced intimal proliferation in allografts. CONCLUSIONS: We found that LMWF treatment reduced intimal thickness and induced the presence of an endothelial cell lining in the vascular graft at 30 days. Our findings may suggest a novel therapeutic strategy in the prevention of TA.

Direct costs associated with lupus nephritis management in the Private Healthcare System in Brazil: an expert panel perspective / Custos diretos associados ao manejo da nefrite lúpica no Sistema de Saúde Privado no Brasil: uma perspectiva segundo painel de especialistas

Objective: To estimate direct medical costs of lupus nephritis (LN) in the Brazilian private healthcare system. Methods: An expert panel of five specialists were convened to discuss health resource usage in LN patient management. The discussion included diagnosis, treatment, and disease monitoring, including dialysis and kidney transplantation. Unit costs (in BRL) were obtained from public sources, and an estimation of 1-year costs was conducted. Results: Approximately 76.0% of patients with LN undergo kidney biopsy, of which 48.1% present with LN classes III­IV and 21.4% have class V. Around 67.5% of patients with LN classes III­IV experience an average of four renal flares annually. Overall, 20.3% of patients present refractory LN, and 10.3% have end-stage kidney disease (ESKD), requiring dialysis and kidney transplantation. Estimated total weighted annual costs per patient were BRL 115,824.81 for LN classes III­IV, BRL 85,684.79 for LN class V, BRL 115,594.98 for refractory LN; and BRL 325,712.88 for ESKD. The main annual cost driver for LN classes III­IV was renal flares (BRL 60,240.41; 52.0%) and dialysis for LN class V (BRL 31,128.38; 36.3%). Conclusions: Total direct costs increase when LN progresses to ESKD. Although it is challenging to improve the diagnosis, identification of the disease at an early stage, together with rapid initiation of treatment, are fundamental elements to optimize results, potentially reducing costs to the system and the impact of disease burden and quality of life on patients.

Objetivo: Estimar os custos médicos diretos da nefrite lúpica (NL) no sistema suplementar de saúde brasileiro. Métodos: Um painel de cinco especialistas foi estruturado para discutir o uso de recursos em saúde no manejo de pacientes com NL. Nesta discussão, incluíram-se o diagnóstico, o tratamento e o monitoramento da doença, contemplando também diálise e transplante renal. Os custos unitários foram obtidos de fontes públicas e os resultados expressos em custo anual. Resultados: Aproximadamente 76,0% dos pacientes com NL são submetidos à biópsia renal, sendo 48,1% com NL de classes III-IV e 21,4% de classe V. Cerca de 67,5% dos pacientes com classes III-IV apresentam, aproximadamente, quatro flares renais anuais. No geral, 20,3% dos pacientes apresentam NL refratária e 10,3% desenvolvem doença renal terminal (DRT), necessitando de diálise e transplante renal. O custo ponderado anual estimado por paciente foi de R$ 115.824,81 para NL de classes III-IV, R$ 85.684,79 para classe V, R$ 115.594,98 para NL refratária e R$ 325.712,88 para DRT. O principal fator para incremento dos custos anuais para NL de classes III-IV foram os flares renais (R$ 60.240,41; 52,0%) e, na classe V, a diálise (R$ 31.128,38; 36,3%). Conclusões: Há um incremento dos custos diretos da NL na progressão para DRT. Embora seja desafiador melhorar o diagnóstico, a identificação da doença em uma fase precoce, aliada ao tratamento iniciado de forma célere, são elementos fundamentais para otimizar os resultados, potencialmente reduzindo os custos ao sistema e o impacto da carga da doença e qualidade de vida dos pacientes.

Determination of suspected fragrance allergens extended list by two-dimensional gas chromatography-mass spectrometry in ready-to-inject samples.

A new strategy was developed to elucidate and quantify 56 (69 analytes including isomers) suspected chemically defined fragrance allergens in perfumes that were recently targeted by the Scientific Committee on Consumer Safety (SCCS). Samples were analyzed with a two-dimensional gas chromatography-quadrupole mass spectrometry system (GC-GC-MS). Method performance was evaluated by the accuracy profile approach to determine uncertainties around the regulation limit of 10mg/kg. This strategy was finally applied to 62 commercialized perfumes, analyzed in the routine workflow. Depending on the matrix, an acceptable result was obtained for 88-100% of the target analytes, which means that results were accurately defined under or above 10mg/kg. This method saves considerable time for complete analysis and could be adopted for routine analysis due to its ruggedness and cost effectiveness.

Collaborative validation of the quantification method for suspected allergens and test of an automated data treatment.

Previous publications investigated different data treatment strategies for quantification of volatile suspected allergens by GC/MS. This publication presents the validation results obtained on "ready to inject" samples under reproducibility conditions following inter-laboratory ring-testing. The approach is based on the monitoring of three selected ions per analyte using two different GC capillary columns. To aid the analysts a decisional tree is used for guidance during the interpretation of the analytical results. The method is evaluated using a fragrance oil concentrate spiked with all suspected allergens to mimic the difficulty of a real sample extract or perfume oil. At the concentrations of 10 and 100mg/kg, imposed by Directive 76/768/EEC for labeling of leave-on and rinse-off cosmetics, the mean bias is +14% and -4%, respectively. The method is linear for all analytes, and the prediction intervals for each analyte have been determined. To speed up the analyst's task, an automated data treatment is also proposed. The method mean bias is slightly shifted towards negative values, but the method prediction intervals are close to that resulting from the decisional tree.