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Alterations in nutritional status, in particular sarcopenia, have been extensively associated with a poor prognosis in cirrhotic patients regardless of the etiology of liver disease. Less is known about the predictive value of myosteatosis, defined as pathological fat infiltration into the skeletal muscle. We retrospectively analyzed a cohort of 151 cirrhotic patients with unresectable hepatocellular carcinoma (HCC) who underwent their first trans-arterial embolization (TAE) between 1 March 2011 and 1 July 2019 at our Institution. Clinical and biochemical data were collected. Sarcopenia was assessed using the L3-SMI method while myosteatosis with a dedicated segmentation suite (3D Slicer), using a single slice at an axial plane located at L3 and calculating the IMAC (Intramuscular Adipose Tissue Content Index). The sex-specific cut-off values for defining myosteatosis were IMAC > −0.44 in males and >−0.31 in females. In our cohort, 115 (76%) patients were included in the myosteatosis group; 128 (85%) patients had a coexistent diagnosis of sarcopenia. Patients with myosteatosis were significantly older and showed higher BMI than patients without myosteatosis. In addition, male gender and alcoholic- or metabolic-related cirrhosis were most represented in the myosteatosis group. Myosteatosis was not associated with a different HCC burden, length of hospitalization, complication rate, and readmission in the first 30 days after discharge. Overall survival was not influenced by the presence of myosteatosis.

Background : Accurate risk stratification of critically ill patients with coronavirus disease 2019 (COVID-19) is essential for optimizing resource allocation, delivering targeted interventions, and maximizing patient survival probability. Machine learning (ML) techniques are attracting increased interest for the development of prediction models as they excel in the analysis of complex signals in data-rich environments such as critical care. Methods : We retrieved data on patients with COVID-19 admitted to an intensive care unit (ICU) between March and October 2020 from the RIsk Stratification in COVID-19 patients in the Intensive Care Unit (RISC-19-ICU) registry. We applied the Extreme Gradient Boosting (XGBoost) algorithm to the data to predict as a binary outcome the increase or decrease in patients’ Sequential Organ Failure Assessment (SOFA) score on day 5 after ICU admission. The model was iteratively cross-validated in different subsets of the study cohort. Results : The final study population consisted of 675 patients. The XGBoost model correctly predicted a decrease in SOFA score in 320/385 (83%) critically ill COVID-19 patients, and an increase in the score in 210/290 (72%) patients. The area under the mean receiver operating characteristic curve for XGBoost was significantly higher than that for the logistic regression model {0.86 vs. 0.69, P

Liver abscess is a rare condition, associated with significant in-hospital mortality. Due to improved diagnostic yield and standardized treatment strategies, mortality has been reduced from 70% to 6% in the last decades.

Introduction. In the last years, many improvements were made to know better in laboratory medicine the total testing process (TTP) including the pre and post analytical phases. To date, however, laboratory common protocols do not extensively applied for the routine testing. Issue is worse for new potential biomarkers in clinical practice owing to timeliness of market entry and the urgent need to adopt new diagnostic tools. Our work conducted to investigate diagnostic pitfalls of new acute kidney injury (AKI) biomarkers with specific observations on the pre/post analytical features of neutrophil gelatinase-associated lipocalin (NGAL) and tissue inhibitor of metalloproteinase 2▪insulin-like growth factor binding protein 7 (TIMP-2)▪(IGFBP-7). Material and Methods. We analysed from previous two studies the urinary samples collected in intensive care unit (ICU) from an adult population undergoing cardiac surgery. Diagnostic accuracy of NGAL and (TIMP-2)▪(IGFBP-7) was determined on urinary samples. For NGAL biomarker the evaluation of two consecutive testing results was introduced. We performed measurements using a chemiluminescent method on an automatic analytical platform and a point of care testing (POCT) Nephrocheck meter. Analysis of biochemical results was performed without and with the urine creatinine (uCrea) correction. Furthermore, a method to calculate the mean variation rate was applied for different biomarker concentrations using differential equations. Results. A received operating curve for predicting AKI was obtained with AUC value= 0.66 corresponding to the better cut-off= 29 ng/mL (p=0.016). A significant association between the NGAL increase and AKI severity was achieved (p=0.02). NGAL increases showed: NGAL pre=18.3 (7.7-23.7) ng/mL, NGAL post= 19.2 (3.8-86) ng/mL median (interquartile range) statistically not significant. Analyzing the corresponded urinary creatinine (N=41), we highlighted that 38/41 had uCrea≤ 50mg/dL suggesting a possible dilution of patient samples collected. Nephrocheck AKI score cut-off=0.3, used in clinical studies, does not evaluate biomarker increase pre/post-surgery. Correction with the urinary creatinine does not have added significant outcomes. However, measure unit of (TIMP-2)▪(IGFBP-7) expressed as AKI score (ng/mL) 2 /1000 introduces a variation due to the amplification of TTP errors. Differential equations applied to Nephrocheck test results demonstrated a mean variation rate that rises as the biomarker concentration increases. Conclusions: NGAL results on urinary testing had a poor diagnostic accuracy probably due to pre-analytical variability in ICU critical patients. Pre and Post-analytical variability affected Nephrocheck results as suggested by the non-linear expression of measurements. In addition, the too tight and low AKI score reference range (0.02-0.3) may determine possible overlap between different patient groups.

Background Coronavirus disease 2019 (COVID-19) is associated with a high disease burden with 10% of confirmed cases progressing towards critical illness. Nevertheless, the disease course and predictors of mortality in critically ill patients are poorly understood. Methods Following the critical developments in ICUs in regions experiencing early inception of the pandemic, the European-based, international RIsk Stratification in COVID-19 patients in the Intensive Care Unit (RISC-19-ICU) registry was created to provide near real-time assessment of patients developing critical illness due to COVID-19. Findings As of April 22, 2020, 639 critically ill patients with confirmed SARS-CoV-2 infection were included in the RISC-19-ICU registry. Of these, 398 had deceased or been discharged from the ICU. ICU-mortality was 24%, median length of stay 12 (IQR, 5-21) days. ARDS was diagnosed in 74%, with a minimum P/F-ratio of 110 (IQR, 80-148). Prone positioning, ECCO2R, or ECMO were applied in 57%. Off-label therapies were prescribed in 265 (67%) patients, and 89% of all bloodstream infections were observed in this subgroup (n = 66; RR=3·2, 95% CI [1·7-6·0]). While PCT and IL-6 levels remained similar in ICU survivors and non-survivors throughout the ICU stay (p = 0·35, 0·34), CRP, creatinine, troponin, d-dimer, lactate, neutrophil count, P/F-ratio diverged within the first seven days (p

Abstract: Despite the technological advancements in the last 40 years, conditions such as refractory cardiogenic shock and cardiac arrest still present a very high mortality rate in real-world clinical practice. In this light, we have reviewed the techniques, indications, contraindications, and results of the socalled Veno-Arterial Extracorporeal Circulatory Membrane Oxygenation (VA-ECMO) in the adult population to evaluate the current results of this temporary cardio-pulmonary support as salvage and/or bridge therapy in the patient suffering from refractory cardiogenic shock or cardio-circulatory arrest. The results are encouraging, especially in the setting of refractory cardiogenic shock and in-hospital cardiac arrest. Among a selected population, the prompt institution of a VA-ECMO may radically change the prognosis by sustaining vital functions while looking for the leading cause or waiting for the reversal of the temporary cardio-respiratory negative condition. The future directions aim to standardized and shared protocols, miniaturization of the machines, and possibly the institution of specialized “ECMO teams” for in and the out-of-hospital institution of the tool.

Background. Accumulating evidence suggests that inflammation plays a key role in acute kidney injury (AKI) pathogenesis. We explored the relationship between high-sensitivity C-reactive protein (hs-CRP) and AKI in acute myocardial infarction (AMI). Methods. We prospectively included 2,063 AMI patients in whom hs-CRP was measured at admission. AKI incidence and a clinical composite of in-hospital death, cardiogenic shock, and acute pulmonary edema were the study endpoints. Results. Two-hundred-thirty-four (11%) patients developed AKI. hs-CRP levels were higher in AKI patients (45 ± 87 vs. 16 ± 41 mg/L, p &lt, 0.0001). The incidence and severity of AKI, as well as the rate of the composite endpoint, increased in parallel with hs-CRP quartiles (p for trend &lt, 0.0001 for all comparisons). A significant correlation was found between hs-CRP and the maximal increase of serum creatinine (R = 0.23, 0.0001). The AUC of hs-CRP for AKI prediction was 0.69 (p &lt, 0.001). At reclassification analysis, addition of hs-CRP allowed to properly reclassify 14% of patients when added to creatinine and 8% of patients when added to a clinical model. Conclusions. In AMI, admission hs-CRP is closely associated with AKI development and severity, and with in-hospital outcomes. Future research should focus on whether prophylactic renal strategies in patients with high hs-CRP might prevent AKI and improve outcome.

Background In acute myocardial infarction, acute hyperglycemia is a predictor of acute kidney injury ( AKI ), particularly in patients without diabetes mellitus. This emphasizes the importance of an acute glycemic rise rather than glycemia level at admission. We investigated whether, in diabetic patients with acute myocardial infarction, the combined evaluation of acute and chronic glycemic levels may have better prognostic value for AKI than admission glycemia. Methods and Results At admission, we prospectively measured glycemia and estimated average chronic glucose levels (mg/dL) using glycosylated hemoglobin (HbA 1c ), according to the following formula: 28.7×HbA 1c (%)−46.7. We evaluated the association with AKI of the acute/chronic glycemic ratio and of the difference between acute and chronic glycemia (Δ A−C ). We enrolled 474 diabetic patients with acute myocardial infarction. Of them, 77 (16%) experienced AKI . The incidence of AKI increased in parallel with the acute/chronic glycemic ratio (12%, 14%, 22%; P =0.02 for trend) and Δ A−C (13%, 13%, 23%; P =0.01) but not with admission glycemic tertiles ( P =0.22). At receiver operating characteristic analysis, the acute/chronic glycemic ratio (area under the curve: 0.62 [95% confidence interval, 0.55–0.69]; P =0.001) and Δ A−C (area under the curve: 0.62 [95% confidence interval, 0.54–0.69]; P =0.002) accurately predicted AKI , without difference in the area under the curve between them ( P =0.53). At reclassification analysis, the addition of the acute/chronic glycemic ratio and Δ A−C to acute glycemia allowed proper AKI risk prediction in 16% of patients. Conclusions In diabetic patients with acute myocardial infarction, AKI is better predicted by the combined evaluation of acute and chronic glycemic values than by assessment of admission glycemia alone.

El artículo presenta un ensayo de historia visual sobre la misión evangélica indígena de Embarcación (Salta), formada por misioneros escandinavos durante la década de 1920. Interesa avanzar en el conocimiento sobre los procesos de cambio sociorreligioso entre los pueblos indígenas del Chaco argentino asumiendo la positividad que aporta la evidencia fotográfica. Amparados en la indagación etnográfica en la zona y en el examen del archivo de la Misión Evangélica Asamblea de Dios de Embarcación, el estudio selecciona un conjunto de imágenes que los misioneros realizaron durante medio siglo, entre 1925 y 1975. El trabajo examina las marcas de enunciación visual presentes en las fotografías, delimitando sus principales núcleos temáticos con el objeto de vislumbrar regularidades e innovaciones atestiguadas en el proceso histórico de la misionalización escandinava entre parcialidades wichí y toba. Como hipótesis rectora sostenemos que la imbricación entre evangelización protestante, representación fotográfica y discursos de la alteridad indígena presentó continuidades y divergencias en la dinámica histórica de la misión, signadas por los cambios institucionales, territoriales y de liderazgo a la cual estuvo sujeta. Tres partes organizan el trabajo. La primera refiere un breve análisis comparado sobre el rol de las imágenes en las empresas misioneras chaqueñas. La segunda una descripción contextualizada del archivo fotográfico y su proceso social concomitante. La tercera, y más amplia, expone el itinerario histórico visual por las dos etapas que definieron el derrotero de esta experiencia, la “misión vieja” (1935-1961) y Misión La Loma (1962-actualidad). The article is an essay in visual history about the indigenous evangelical mission of Embarcación (Salta), created by Scandinavian missionaries during the 1920s. It proposes to advance in the knowledge of the sociorreligious change among the indigenous peoples of the Argentine Chaco, assuming the positivity provided by photographic evidence. Based on ethnographic research in the area and the examination of the archives of the Evangelical Mission Assembly of God of Embarcación, the study selects a set of images that the missionaries made during half a century between 1925 and 1975. The work examines the visual enunciation present in the photographs, delimiting its main thematic core in order to glimpse regularities and innovations attested in the historical process of the Scandinavian missionalization between Wichí and Toba. As a guiding hypothesis we hold that the interplay between Protestant evangelization, photographic representation and discourses of indigenous alterity presented continuities and divergences in the historical dynamics of the mission, marked by the territorial changes and leadership to which it was subjected. Three sections organize the work. The first refers to a brief comparative analysis of the role of images in the Chaco missionary enterprises. The second is a contextualized description of the photographic archive and its concomitant social process. The third, and broader, exposes the visual historical itinerary by the two stages that defined the course of this experience, the "old mission" (1935-1961) and Mission La Loma (1962-present). Fil: Ceriani Cernadas, César Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15; Argentina. Facultad Latinoamericana de Ciencias Sociales; Argentina Fil: Lavazza, Victor Hugo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15; Argentina. Ministerio de Salud. Instituto Nacional de Medicina Tropical; Argentina

In recent decades, the use of radiopharmaceuticals in the assessment of hepatocellular carcinoma (HCC) has become established, and new findings indicate that radiolabelled choline has considerable potential in this setting. Therefore, in this study we aimed to assess the diagnostic role of 11C-choline positron emission tomography (PET)/CT, compared with conventional imaging with CT/MRI, in patients with HCC. The study population comprised 45 patients (male to female ratio = 37:8, median age 70.5 years) referred to our institution owing to HCC: 27 at initial diagnosis and 18 for restaging after recurrence. In all cases we performed whole-body 11C-choline PET/CT and compared its findings with contrast-enhanced CT (n = 35) or MRI (n = 29) or both (n = 15) for a total of 50 paired scans. The reference standard was either histological proof (21 patients) or a multidisciplinary consensus. Diagnostic accuracy was then determined in a scan-based (SBA) and a lesion-based analysis (LBA). On SBA the sensitivity and specificity for PET were 88 and 90 %, respectively, whereas for CT/MRI they were 90 and 73 %, respectively (p > 0.05). On LBA the overall sensitivity and specificity were 78 and 86 %, respectively, for PET vs 65 and 55 % for CT/MRI. Overall we investigated 168 disease sites, of which 100 were in the liver and 68 were extrahepatic. When considering only liver lesions, 11C-choline PET and CT/MRI showed an accuracy of 66 and 85 %, respectively, while for extrahepatic lesions PET showed an accuracy of 99 %, while the accuracy of CT/MRI was 32 %. In both cases, there was a statistically significant difference in accuracy between the two modalities (p

Models based on logistic regression analysis are proposed as noninvasive tools to predict cirrhosis in chronic hepatitis C (CHC) patients. However, none showed to be sufficiently accurate to replace liver biopsy. Artificial neural networks (ANNs), providing a prediction based on nonlinear algorithms, can improve the diagnosis of cirrhosis, a syndrome characterized by complex, nonlinear biological alterations. We compared ANNs with two logistic regression analysis-based models in predicting CHC histologically proven cirrhosis.Liver biopsy was obtained in CHC patients of two different cohorts (an internal cohort including 244 patients and an external cohort including 220 patients). One hundred and forty-four patients from the internal cohort served as a training set to construct ANNs and a logistic regression model (LOGIT). These two models and the aspartate aminotransferase-to-platelet ratio index (APRI) were tested in the remaining 100 patients (internal validation set) and in the external cohort (external validation set). Diagnostic performances were evaluated by standard indices of accuracy.In the internal validation set, ANNs, LOGIT, and APRI showed similar discrimination powers (0.88, 0.87, and 0.87 respectively). However, ANNs showed the best positive predictive value (0.86 vs. 0.67 and 0.56) and positive likelihood ratio (40.2 vs. 13.4 and 8.4). In the external validation set, the discrimination power of ANNs (0.76) was significantly higher than those of LOGIT (0.67) and APRI (0.67).Compared to conventional models, ANNs performance in predicting CHC cirrhosis is slightly better and more reproducible.

Background Little is known about the efficacy, safety and tolerability of pegylated interferon plus ribavirin treatment in patients with chronic hepatitis C virus (HCV) infection and histologically proven fully established cirrhosis. We aimed here to evaluate the safety of this regimen in such patients and to identify baseline and on-treatment predictors of a sustained virological response (SVR). Methods Patients with histologically proven, HCV-induced cirrhosis were randomized to receive pegylated interferon-α2b (PEG-IFN-α2b; 1.0 μg/kg/week, n=56; group A) or recombinant interferon-α2b (IFN-α2b; 3 million IU three times/week, n=36; group B), each in combination with a weight-based dose of ribavirin (800–1,200 mg/day) for up to 48 weeks. The primary endpoint of the study was the assessment of SVR, defined as undetectable HCV RNA 24 weeks after treatment cessation. Results Overall, 40% (37/93) of patients attained SVR: 44% (25/57) in group A and 33% (12/36) in group B ( P=0.31). SVR rates were significantly higher in genotype 2/3 patients than in genotype 1 patients (69% versus 25%; PConclusions PEG-IFN-α2b plus ribavirin for 48 weeks is an efficacious and well-tolerated treatment regimen for patients with HCV-induced cirrhosis. Although SVR rates were more satisfactory in genotype 2/3 than in genotype 1 patients, our study identified additional predictors of response that could allow physicians to better manage treatment in this ‘difficult-to-cure’ subset of patients.

Background The relative impact of perioperative risk profile and postoperative complications on long-term outcome in cardiac surgical patients is currently unclear. The aim of this work was to assess the relative predictive value of the European System for Cardiac Operative Risk Evaluation (EuroSCORE) and Sequential Organ Failure Assessment (SOFA) on long-term event-free survival in this patient population. Methods Preoperative and postoperative variables, EuroSCORE and SOFA, 30-day mortality, and long-term mortality or hospital admission for cardiovascular events were assessed in 115 consecutive cardiac surgical patients in whom multiorgan dysfunction syndrome developed postoperatively. Results Mean age was 70 ± 8 years, 41% were women, EuroSCORE averaged 7.87 ± 3.99, and postoperative stay in the intensive care unit was 10.3 ± 8.2 days. In-hospital 30-day mortality was 10.4% (n = 12). During 1998 person-months follow-up, 12 (11.6%) of 103 patients discharged alive died, and 46 (44.7%) met the combined end point of all-cause death or cardiovascular admission. By Cox multivariate analysis, maximum SOFA (hazard ratio [HR], 2.17; 95% confidence interval [CI], 1.34 to 3.51) and maximum cardiovascular score (HR, 2.35; 95% CI, 1.22 to 4.51) independently predicted all-cause mortality. EuroSCORE (HR, 1.33; 95% CI, 1.01 to 1.76), maximum cardiovascular score (HR 2.09; 95% CI 1.41 to 3.10), and maximum liver score (HR 2.67; 95% CI, 1.46 to 4.86) were independently associated with the combined end point. Conclusions High-risk cardiac surgical patients with postoperative multiorgan dysfunction syndrome show excess mortality and cardiovascular morbidity after hospital discharge. Combined preoperative and postoperative risk stratification identifies patients with the highest likelihood of death or early readmission.

Summary Background Biopsy is the gold standard for assessing cirrhosis in patients with chronic hepatitis C virus infection, but it is expensive and at risk of complications. Alternative non-invasive methods have been developed but their usefulness remains uncertain. Aim To compare the accuracy of five non-invasive scores in detecting cirrhosis. Methods We reviewed the charts and liver biopsies of 228 consecutive, treatment-naive, hepatitis C virus-positive patients, 13.2% of whom with histological diagnosis of cirrhosis. The five alternative scores were age-platelet index, cirrhosis discriminant score, aspartate transaminases to platelet ratio index, Pohl's index, and aspartate transaminases/alanine transaminases ratio. Results The specificities of the scores were good (87–100%), but not so their sensitivities (17–67%). Accordingly positive likelihood ratios were generally good but negative likelihood ratios were suboptimal. Combinations of the scores independently related to cirrhosis only slightly change this diagnostic accuracy. Using double cut-offs to exclude/diagnoses cirrhosis, cirrhosis discriminant score classified 21% of patients without misdiagnoses and aspartate transaminases to platelet ratio index classified 85% of case with 9% of misdiagnoses. Conclusions The five scores showed variable sensitivities and specificities in detecting liver cirrhosis, both individually and in combination. The use of double cut-off points may make the cirrhosis discriminant score and aspartate transaminases to platelet ratio index useful to reduce the number of patients submitted to liver biopsy.

In recent decades, the use of radiopharmaceuticals in the assessment of hepatocellular carcinoma (HCC) has become established, and new findings indicate that radiolabelled choline has considerable potential in this setting. Therefore, in this study we aimed to assess the diagnostic role of (11)C-choline positron emission tomography (PET)/CT, compared with conventional imaging with CT/MRI, in patients with HCC.The study population comprised 45 patients (male to female ratio = 37:8, median age 70.5 years) referred to our institution owing to HCC: 27 at initial diagnosis and 18 for restaging after recurrence. In all cases we performed whole-body (11)C-choline PET/CT and compared its findings with contrast-enhanced CT (n = 35) or MRI (n = 29) or both (n = 15) for a total of 50 paired scans. The reference standard was either histological proof (21 patients) or a multidisciplinary consensus. Diagnostic accuracy was then determined in a scan-based (SBA) and a lesion-based analysis (LBA).On SBA the sensitivity and specificity for PET were 88 and 90 %, respectively, whereas for CT/MRI they were 90 and 73 %, respectively (p 0.05). On LBA the overall sensitivity and specificity were 78 and 86 %, respectively, for PET vs 65 and 55 % for CT/MRI. Overall we investigated 168 disease sites, of which 100 were in the liver and 68 were extrahepatic. When considering only liver lesions, (11)C-choline PET and CT/MRI showed an accuracy of 66 and 85 %, respectively, while for extrahepatic lesions PET showed an accuracy of 99 %, while the accuracy of CT/MRI was 32 %. In both cases, there was a statistically significant difference in accuracy between the two modalities (p 0.01). Combination of the PET results with those of CT/MRI resulted in the highest diagnostic accuracy in both analyses, at 92 % for SBA and 96 % for LBA. In 11 patients (24 %) the PET findings modified the therapeutic strategy, the modification proving appropriate in 10 of them.(11)C-Choline PET showed good accuracy in investigating patients with HCC and prompted a change in treatment planning in almost one fourth of patients. The main strength of (11)C-choline PET/CT resides in its ability to detect extrahepatic HCC localizations, but the combination with conventional imaging modalities allowed for the highest diagnostic accuracy.

Objective: To evaluate myocardial lactate metabolism as a marker of functional status after surgical coronary revascularization. Design: Single-center, prospective, cohort study. Setting: Tertiary care teaching hospital. Participants: Fifty patients with stable angina, ejection fraction >0.40, undergoing coronary artery bypass surgery for multiple-vessel disease. Measurements and main results: Before (T1) and 30 minutes (T2) after coronary artery bypass grafting, the authors simultaneously sampled blood from artery and coronary sinus to determine myocardial lactate dynamics and performed transesophageal echocardiography (TEE) to assess segmental wall motion. Wall motion score index (WMSI) was calculated with an online/offline comparison. At T2, WMSI improved from 1.40 ± 0.31 to 1.17 ± 0.23 (p = 0.0001). Preoperatively, 2 patterns of lactate balance were found: 39 patients were lactate extractors (17% ± 10%) and 11 were lactate producers (−11% ± 11%). At T2, lactate metabolism was shifted towards a pattern opposite to the baseline: delta lactate extraction was −8% ± 16% in extractors at T1 versus 7% ± 9% in producers at T1 (p = 0.003). Changes in WMSI were not correlated with changes in lactate utilization. No single preoperative variable predicted postoperative WMSI or its changes from baseline. Cardiopulmonary bypass (CPB) time was the only significant predictor of postoperative lactate extraction by multivariate regression (r = −0.46, p = 0.001): at T2, patients in the highest CPB time quartile showed frank lactate production (−6% ± 13%) when compared with those in the lowest quartile (15% ± 11%, p = 0.005). However, postoperative WMSI was similar in different CPB time groups. Conclusions: Myocardial lactate metabolism pattern is not associated with functional status before and early after successful coronary revascularization. CPB time was the only significant predictor of postoperative lactate extraction. Measurement of lactate does not appear to be a valuable tool to assess the coupling of myocardial regional function and metabolism in the setting of coronary artery surgery and mild-to-moderate functional impairment.

To the Editor,It is known that there is a high rate of nephrotoxicity with a dosage of 60–120 mg/day of adefovir-dipivoxil (Hepsera®). However, a dosage of 10 mg/day has been found to be safe [1,2]...

Mancomunado bajo el interés de reflexionar sobre la diversidad religiosa en Argentina y los límites o posibilidades de la noción de "monopolio católico", en esta comunicación me interesa introducir en el debate una preocupación sobre los sentidos y usos de categorías que marcan con fuerza nuestros estudios. La idea es centrar en el debate una noción cuyo espectro relacional con la categoría religión es históricamente indiscutido, pero que sin embargo interpela y tensiona a la misma desde distintos frentes: la "espiritualidad". Pocas dudas caben acerca de la ubicuidad que ha adquirido esta categoría en la última década, sea en el discurso cotidiano, mediático o científico en Argentina, Latinoamérica y buena parte del orbe. ¿Qué diferencia podríamos establecer entre diversidad religiosa y pluralismo espiritual? ¿Qué relación se presenta entre el mediáticamente denominado "boom de la espiritualidad" y el supuesto quiebre del monopolio religioso del catolicismo? ¿Qué nos informa esta categoría sobre el proceso social de la Argentina reciente? Lógicamente, este artículo no espera lograr responder todos estos interrogantes, pero sí al menos plantear las posibilidades de su debate para abrir así el juego a la reflexión conjunta. Fil: Ceriani Cernadas, Cesar Roberto. Facultad Latinoamericana de Ciencias Sociales. Sede Académica Argentina Buenos Aires. Programa de Antropología Social y Política; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

We present an 80-year-old woman with hibernating myocardium in the left anterior descending coronary artery (LAD) territory who underwent surgical revascularization and metabolic evaluation of the dysfunctioning segments by microdialysis (microD) technique. Myocardial lactate, pyruvate, and glucose did not show obvious changes throughout the procedure. Conversely, myocardial glycerol and glutamate concentrations markedly increased early after cardioplegic arrest and subsided after weaning from cardiopulmonary bypass (CPB) and recovery of myocardial function. Intraoperative myocardial microD may add relevant pathophysiologic information on hibernating myocardium undergoing coronary flow restoration and, eventually, improve patient care.

Background/Aims: Hepatitis C virus (HCV) easily undergoes genomic changes, thus accounting for the presence of different genotypes, with different geographic distributions and different outcomes of chronic hepatitis. Type 1b is frequently found in advanced diseases; however, since this genotype is the most prevalent in older patients, the association with advanced age and severity of the disease is confounding. The aim of this study was to assess changes in the prevalence of HCV genotypes by surveying a large population of chronic hepatitis C patients in Northern Italy, and to assess if the high prevalence of genotye 1b in older patients with advanced diseases simply reflects the duration of HCV infection, rather than intrinsic biological properties of HCV. Methods: We studied 1368 HCV-RNA positive patients, with histologically proven chronic hepatitis. Drug addiction, blood transfusions and sporadically acquired infections represented the risk factors Results: Genotype 1b, the most prevalent isolate, and genotype 2a were associated with older age, cirrhosis, sporadically-acquired infections and blood transfusion, while types 1a, 3a, and 4 were associated with younger age, chronic persistent hepatitis and drug addiction. Patients with a history of transfusion were divided into four groups depending on the period of transfusion. The prevalence of genotype 1b decreased with time. Type 3a appeared only after 1979. Conclusions: The severity of chronic hepatitis C could be related more to the duration of the infection rather than to the intrinsic pathogenicity of HCV genotypes

deficiency are frequent in white populations. Conflictscribed. The most common allele, PiM, is associated with an ing data on the association of the two conditions and AAT concentration of 1.5 to 3.5 g/L, whereas some other alon the severity of the disease in those in whom these leles are characterized by a defect in AAT secretion and sedisorders coexist have emerged from analyses of small questration of the protein in the hepatocytes. 7 An increased numbers of patients. To determine if the frequency of risk for cirrhosis and hepatocellular carcinoma (HCC) has AAT deficiency is increased in genetic hemochromatobeen reported in subjects homozygous for the rare Z allele, 8-12 sis, we characterized this protein by isoelectric focusing whereas results are conflicting in subjects heterozygous for and DNA analysis in 115 Italian patients with the disease the Z allele and in subjects with other phenotypes. and 290 controls. The frequency of AAT deficiency in Both GH and AAT deficiency are genetically determined patients with genetic hemochromatosis was similar to autosomal recessive disorders common in white populations; that in controls (10% and 9%, respectively). The prevathe estimated prevalence of GH is 1 in 400, and that of AAT lence of cirrhosis in patients with genetic hemochromadeficiency is 1 in 1,600. 13 Thus, the two conditions could coextosis with MM phenotype was 53%, compared with 58% ist even though the gene for GH, still undetected, is located in those with non-MM phenotype; that of hepatocellular on chromosome 6 14 and that for AAT on chromosome 14 7 ; this carcinoma, occurring only in cirrhotic patients, was 22% association could account for more severe forms of GH. and 28%, respectively. In conclusion, the frequency of In the last few years, conflicting data on the coexistence of AAT deficiency was not increased in our large series of GH and AAT deficit have been reported in small groups of Italian patients with genetic hemochromatosis. Patients patients. Eriksson et al. 15 did not find any association bein whom the two defects coexisted did not appear to tween the two conditions in 27 patients with GH, Rabinovitz have a more severe disease, but the limited number of

Little is known about the efficacy, safety and tolerability of pegylated interferon plus ribavirin treatment in patients with chronic hepatitis Cvirus (HCV) infection and histologically proven fully established cirrhosis. We aimed here to evaluate the safety of this regimen in such patients and to identify baseline and on-treatment predictors of a sustained virological response (SVR).Patients with histologically proven, HCV-induced cirrhosis were randomized to receive pegylated interferon-alpha2b (PEG-IFN-alpha2b; 1.0 microg/kg/week, n=56; group A) or recombinant interferon-alpha2b (IFN-alpha2b; 3 million IU three times/week, n=36; group B), each in combination with a weight-based dose of ribavirin (800-1,200 mg/day) for up to 48 weeks. The primary endpoint of the study was the assessment of SVR, defined as undetectable HCV RNA 24 weeks after treatment cessation.Overall, 40% (37/93) of patients attained SVR: 44% (25/57) in group A and 33% (12/36) in group B (P=0.31). SVR rates were significantly higher in genotype 2/3 patients than in genotype 1 patients (69% versus 25%; P0.0001). Platelet count at baseline, rapid virological response, and early virological response were predictors of SVR. Twelve patients discontinued treatment because of an adverse event and 20 patients required ribavirin dose reduction for the management of anaemia.PEG-IFN-alpha2b plus ribavirin for 48 weeks is an efficacious and well-tolerated treatment regimen for patients with HCV-induced cirrhosis. Although SVR rates were more satisfactory in genotype 2/3 than in genotype 1 patients, our study identified additional predictors of response that could allow physicians to better manage treatment in this 'difficult-to-cure' subset of patients.

Hyperferritinemia, a common feature of nonalcoholic fatty liver disease (NAFLD), has been associated with steatohepatitis and fibrosis. Heterozygosity for alpha 1-antitrypsin (AAT) mutations is a cofactor of liver damage, and AAT influences inflammation and iron metabolism. This study evaluated the prevalence of the common AAT PiS/PiZ mutants in 353 patients with NAFLD, 195 of whom had hyperferritinemia, versus 114 matched controls and their influence on iron metabolism and the severity of liver damage in the 212 patients submitted to biopsy. PiS and PiZ alleles were searched for by restriction analysis. Thirty-eight patients (10.8%) carried non-MM genotypes versus 4/114 (3.5%) controls (P = .02). Patients carrying AAT mutations had higher ferritin (573 [454-966] vs. 348 [201-648]; P = .001) with similar transferrin saturation. The difference was more evident in males (P < .0001) and significant in patients not carrying HFE genotypes associated with iron overload (P = .015). The prevalence of non-MM genotypes was higher in patients with hyperferritinemia than in those without (28/195, 14% vs. 10/158, 6%, P = .016), and AAT mutations were associated with higher prevalence of sinusoidal siderosis (17/27, 63% vs. 70/180, 39%; P = .02), and sinusoidal/total iron score (46.3 +/- 38% vs. 25.1 +/- 35%, P = .01). Although ferritin was independently associated with fibrosis (P = .047), AAT mutations favoring sinusoidal iron deposition did not affect liver damage. In conclusion, AAT mutations are associated with hyperferritinemia and sinusoidal iron accumulation, but not with more severe liver damage in NAFLD.

To assess the applicability of the sequential organ failure assessment (SOFA) score to cardiac surgical patients.Observational cohort study.Adult cardiac surgical ICU.Two hundred eighteen patients requiring ICU stay96 h.The SOFA score was calculated daily until ICU discharge. Derived SOFA variables-total maximum SOFA (TMS), DeltaSOFA, maximum SOFA (maxSOFA), and DeltamaxSOFA-were considered. Length of ICU stay was 8.9 +/- 6.7 days (mean +/- SD). The mortality rate was 11.0% in the ICU and 15.6% in the hospital. Nonsurvivors had higher TMS, DeltaSOFA, single-organ system, and mean total scores on day 1 (9.8 +/- 2.5 vs 7.8 +/- 2.3, p0.05) and thereafter until day 10. The total SOFA score on the first 10 days of ICU stay, time, survival status, and their interaction were all significant (p0.001), with higher SOFA scores for nonsurvivors, and lower scores for survivors that decreased as the number of days from operation increased. Cardiovascular score on day 1 carried the highest relative risk of mortality among other systems (risk ratio [RR], 2.12; 95% confidence interval [CI], 1.31 to 3.45; p0.01), as did maximum cardiovascular score (RR, 2.81; 95% CI, 1.62 to 4.85; p0.001). A growing number of failing organs was associated with mortality, from the first to the sixth postoperative day (p0.05). Total score on day 1, TMS, DeltaSOFA, maxSOFA, and DeltamaxSOFA were reliable predictors of mortality with area under receiver operating characteristic curve of 0.71 (SE, 0.08), 0.89 (SE, 0.05), 0.86 (SE, 0.06), 0.88 (SE, 0.05), and 0.88 (SE, 0.06), respectively. Length of hospital stay was significantly associated (p = 0.05) to TMS and DeltaSOFA and not to other SOFA scores, age, or sex.The SOFA score may be used to grade the severity of postoperative morbidity in cardiac surgical patients without specific adaptations. The model identifies patients at increased risk for postoperative mortality.

Background/Aims : The best treatment for chronic hepatitis C patients who do not respond to interferon is still unknown. Reported rates of response to treatment vary as the result of heterogeneous definitions of non-responders and small study size. Methods : One hundred nineteen hepatitis C virus (HCV) RNA-positive non-responders to high-dose interferon monotherapy received alpha-interferon, 5 MU tiw plus oral ribavirin, 1000–1200 mg/day for 48 weeks (Group A, n =74) or alpha-interferon, 5 MU daily for 4 weeks, followed by 5 MU tiw plus oral ribavirin, 1000–1200 mg/day for 44 weeks (Group B, n =45) according to the Institution where they were followed. Persistently normal alanine aminotransferase and negative HCV RNA up to 72 weeks from treatment onset defined a sustained response. Results : Eighteen patients discontinued treatment (13 developed anemia, two mucositis, one granulocytopenia; two were dropouts), none for serious adverse events. There were 24 (20%) sustained responders, with similar final response rates in Groups A and B. Sustained response was more frequent in patients aged ≤40 years (36% vs. 13%; P =0.006) and in those with non-1 genotype (44% vs. 14%; P =0.002). Among genotype 1 patients, the younger ones showed higher response rates (32% vs. 7%; P =0.005). Compared with patients harboring non-1 genotypes, the odds ratio of being a non-responder was 1.68 (confidence interval (CI): 0.53–5.37; P =0.381) in younger genotype 1 patients and 9.53 (CI: 2.84–32; P Conclusions : Chronic hepatitis C patients who are non-responders to interferon monotherapy and infected by non-1 genotypes should undergo re-treatment with combination therapy. Treatment should be extended to younger genotype 1 patients who are more susceptible to liver disease worsening because of longer life expectancy and have a higher probability of being long lasting responders than their older counterparts.

It has been suggested that iron depletion improves the response to interferon in patients with chronic hepatitis C. We aimed to evaluate whether iron reduction by phlebotomy before interferon improves the rate of virological sustained response in previously untreated noncirrhotic patients.One hundred fourteen hepatitis C virus (HCV) RNA positive patients with hepatic iron concentrations ofor =700 microg/g dry wt (men) andor =500 microg/g dry wt (women), stratified according to HCV genotype and gamma-glutamyltransferase values, were randomly allocated to interferon alone (6 MU three times a week) (group A) or to phlebotomy until iron depletion followed by interferon (6 MU three times a week) (group B). After 4 months dosage was reduced to 3 MU three times a week for another 8 months.Virological sustained response was observed in 25 patients (22%), nine (15.8%, 95% CI = 7.5-27.9) of group A and 16 (28.1%, 95% CI = 17.0-41.6) of group B. At univariate analysis the variables associated with the response were HCV genotypes 2-3, normal gamma-glutamyltransferase, higher levels of baseline ALT, normal ALT values, and negativity for HCV-RNA at the 3rd month of therapy. At multivariate analysis, genotype and ALT levels at enrollment maintained their association with the response. A trend toward a better response to interferon was observed in patients who received phlebotomy (odds ratio = 2.32, 95% CI = 0.96-6.24, p = 0.082). Patients with hepatic iron concentration ofor = 1100 microg/g dry wt had a trend toward a higher rate of virological sustained response (p = 0.059) when submitted to treatment B.Iron removal by phlebotomy is able to improve the rate of response to interferon, especially in patients with lower hepatic iron deposits; it could be useful as adjuvant therapy to new therapeutic modalities.

High hepatocyte proliferation has been recently proposed as a risk factor for the development of hepatocellular carcinoma (HCC). The aim of this study was to assess whether hepatocyte proliferation is an independent risk factor for HCC when considered together with clinical and demographic characteristics.We retrospectively evaluated 97 consecutive patients with a histological diagnosis of cirrhosis and preserved liver function, enrolled in a surveillance program for early diagnosis of HCC. Hepatocyte proliferation was evaluated by flow-cytometric analysis in liver samples collected at the time of histological diagnosis of cirrhosis. All patients were followed with abdominal US and serum alpha-fetoprotein (AFP) assays every 6 months.During a mean follow-up of 53 months (range, 12-120 months), 12 patients developed HCC, giving an annual incidence of 2.8%. The mean S-phase fraction was 2.5%+/-1.6 in patients who developed HCC and 0.9%+/-0.6 in those who did not (p0.0001). By univariate analysis, S-phase fraction 1.8% or higher and AFP higher than 20 ng/ml were the only two variables significantly correlated with the development of HCC (p0.0001, p0.0001). Multivariate analysis found that both variables were independently associated with HCC development (p0.003 and p0.005, respectively), with hazard ratios of 8.0 and 7.3 (confidence intervals, 2.1-31.2 and 1.8-29.2). Among patients with high AFP and/or high S-phase fraction, 11 (39%) developed HCC, compared with only one (1%) with a low S-phase fraction and normal AFP, corresponding to HCC yearly incidences of 9.5% and 0.3% (p0.00009).Patients with high S-phase fraction and/or above-normal serum AFP are at higher risk of developing HCC and should be offered a close surveillance program.

Most patients with serum hepatitis C virus (HCV) RNA and persistently normal alanine transaminase (ALT) levels show histological features of mild to moderately active chronic hepatitis. Some cirrhosis has also been reported. To assess whether interferon (IFN) treatment led to long-term HCV suppression in these patients, 31 previously untreated patients (15 men, 16 women; mean age, 44 years) with serum HCV RNA, persistently normal ALT levels on at least four consecutive occasions 2 months apart, and histological features of chronic hepatitis (21 mild activity, 10 moderate activity) were randomized to receive 1FN-alpha-2a, 3 MU three times a week for 6 months (n = 16), or no treatment (n = 15). All patients were followed up for at least 6 months after treatment ended. HCV RNA was tested by nested reverse-transcription polymerase chain reaction (RT-PCR) using 5'-untranslated region complementary primers, quantified by branched-DNA assay, and typed by nested RT-PCR testing for the HCV core region. Treated and untreated patients had similar epidemiological, virological, and histological characteristics. At the end of treatment, serum HCV RNA was still detected in 15 patients (94%) and 14 controls (93%). ALT levels flared up in 10 patients receiving IFN (62%) and in 1 control (62% vs. 7%; P.005, chi2 test). In conclusion, 6 months' treatment with IFN-alpha-2a did not eradicate HCV RNA from serum in carriers with persistently normal ALT levels but caused ALT flare-ups in two thirds of them. Until more is known about the natural history of HCV RNA carriers with normal ALT levels, these patients should not be treated with IFN.

Radioimmunolocalization for detection or therapy of breast cancer has undergone only limited investigation. Successful targeting of breast tumors with radiolabeled antibodies has awaited the identification of the optimal antigen targets, the appropriate antibodies, as well as the linking chemistry necessary to produce stable radioimmunoconjugates. Radioimmunodetection trials in breast cancer have employed both the intravenous and interstitial administration routes. Sensitivity of intravenously administered immunoconjugates for metastatic disease has ranged from 50-78% in small series of patients 1-3. The antibodies used in these trials were directed against various breast cancer associated antigens including human milk fat globule membrane (HMFG) or breast epithelial mucin and CEA. Excellent sensitivity for primary breast tumors using an antibody directed against TAG-72 has been reported3, but in the same patients