Tumor M2-Pyruvate Kinase, a New Metabolic Marker for Pancreatic Cancer

An isoenzyme of pyruvate kinase (Tu M2-PK) is overexpressed by tumor cells and can be measured in blood by a specific immunoenzymatic assay. Our objective was to investigate the diagnostic value of Tu M2-PK in comparison with that of CA 19-9 in pancreatic cancer. We studied 265 subjects: 60 with histologically confirmed pancreatic cancer, 43 with benign pancreatic diseases (acute and chronic pancreatitis), 5 with benign cystic neoplasms of the pancreas, 9 with neuroendocrine tumors, 77 with other abdominal malignancies, 47 with benign digestive diseases, and 24 healthy controls. Levels of plasma Tu M2-PK and serum CA 19-9 were determined by commercially available specific immunoassays. The diagnostic sensitivity and specificity of Tu M2-PK for pancreatic cancer were 85 and 41%, respectively, while those of CA 19-9 were 75 and 81%. The combination of the two tests significantly increased sensitivity (97%) but lowered specificity (38%). In discriminating between pancreatic cancer and acute or chronic pancreatitis, Tu M2-PK turned out to be less accurate than CA 19-9. In patients without pancreatic tumor, cholestasis appeared not to affect the values of Tu M2-PK, while CA 19-9 was found to be significantly higher. Tu M2-PK was also abnormally high in the majority of patients with other digestive malignancies or neuroendocrine tumors. The results demonstrate that Tu M2-PK has a satisfactory sensitivity but a poor specificity in the diagnosis of pancreatic cancer. Used together with CA 19-9, the sensitivity increases considerably.     

Persistent elevation of serum CA 19-9 with no evidence of malignant disease

BackgroundSerum CA 19-9 is the mainstay marker for the diagnosis of biliopancreatic malignancies, though a persistent elevation can also be observed in various benign diseases.AimsIn this study, a marked increase of serum CA 19-9 was seen in 10 patients who had no evidence of malignant disease. The possible causes of this finding are discussed.PatientsNine women and one man were studied, whose admitting diagnoses were as follows: pulmonary fibrosis in two, diabetes in two, non-ulcer dyspepsia in two, obesity in one, acute diarrhoea in one, colon diverticula in one and gastric ulcer in one.MethodsRoutine blood tests, tumour marker determinations, imaging studies and endoscopy were carried out at admission.ResultsSerum CA 19-9 levels ranged from 112 to 1338 IU/ml (mean 517 IU/ml). Abdominal ultrasonography, CT-scan, upper gastrointestinal X-ray series and gastrointestinal endoscopies were negative for malignancy. During the follow-up period (range 2–7 years) serum CA 19-9 values were persistently elevated in all patients.ConclusionsOur study shows that persistent and significant elevation of serum CA 19-9 can be found in non-malignant and non-cholestatic disease.     

Valor pronóstico del margen quirúrgico positivo tras la resección de un colangiocarcinoma. Experiencia en un centro de alto volumen en cirugía hepatopancreatobiliar

Introduction and aimsCholangiocarcinoma accounts for 3% of gastrointestinal tumors and is the second most frequent hepatic neoplasia after hepatocellular carcinoma. The primary aim was to evaluate the median disease-free period and survival in patients with cholangiocarcinoma diagnosis through the comparison of R0 and R1 resection margins.Material and methodsA retrospective analysis was conducted on 36 patients that underwent some type of surgical resection due to cholangiocarcinoma diagnosis, within the time frame of 2000-2017, at a center specializing in hepatopancreatobiliary surgery. Population, preoperative, and oncologic variables were included. The IBM Statistical Package for the Social Sciences for Mac, version 16.0, software (IBM SPSS Inc., Chicago, IL, USA) was employed.ResultsThirty-one patients underwent hepatectomy, the Whipple procedure, or bypass surgery, depending on tumor location. The statistical significance of survival between patients with positive margins and those with negative margins was evaluated through the Mann-Whitney U test, with a P < .05 as the reference value. No statistically significant difference was found. The overall morbidity rate was 58.06% (n = 18) and the mortality rate was 12.9% (n = 4).ConclusionsNo statistically significant difference in relation to the incidence of disease recurrence or general survival resulted from the comparison of microscopically positive surgical margins (R1) and negative surgical margins (R0). There was also no correlation between preoperative CA 19-9 levels and disease prognosis.     

Resected biliary tract cancers: A novel clinical–pathological score correlates with global outcome

BackgroundBiliary tract cancer presents a poor prognosis.AimsThe objective of this study is to find clinical-laboratory parameters like prognostic factors to select patients who can benefit from surgery and post-operative treatments.MethodsBetween 2005 and 2010, 41 patients underwent radical surgery at our Institution.A novel score was retrospectively calculated assigning a grade to the clinical-laboratory findings at diagnosis. 0 and 1 point were respectively assigned to the normal or abnormal parameter. Two groups were identified: SCORE 0 and SCORE 1.ResultsPatients with cholangiocarcinoma or Klatskin tumours or asymptomatic at diagnosis presented a significantly better overall survival (OS) than patients with different primary sites or who presented pain, jaundice or cholangitis. At univariate analysis, high levels of aspartate aminotransferase, alanine aminotransferase and CA19-9 before surgery, hyperbilirubinemia before and after surgery had a negative correlation with OS. A worse OS was observed in patients with a higher score (median OS in the “score 0” group = 30.79 months vs. median OS in the “score 1” = 17.98 months).ConclusionOur results suggest that pre and post-surgery clinical-laboratory parameters and the novel score, could be useful, especially for intrahepatic tumours, in predicting the outcome in patients undergoing surgery and in selecting patients to receive adjuvant therapy.     

Perfil clínico y evolución de la amiloidosis cardiaca en un centro español de referencia

Introduction and objectivesCardiac amyloidosis (CA) is produced by amyloid fiber deposition in the myocardium. The most frequent forms are those caused by light chains (AL) and transthyretin (ATTR). Our objective was to describe the diagnosis, treatment and outcomes of CA in a specialized Spanish center.MethodsWe included all patients diagnosed with CA in Hospital Universitario Puerta de Hierro Majadahonda from May 2008 to September 2018. We analyzed their clinical characteristics, outcomes, and survival.ResultsWe included 180 patients with CA, of whom 64 (36%) had AL (50% men; mean age, 65 ± 11 years) and 116 had ATTR (72% men; mean age 79 ± 11 years; 18 with hereditary ATTR). The most common presentation was heart failure in both groups (81% in AL and 45% in ATTR, P < .01). Other forms of presentation in ATTR patients were atrial arrhythmias (16%), conduction disorders (6%), and incidental finding (6%); 70 patients (40%), had a previous alternative cardiac diagnosis. Diagnosis was noninvasive in 75% of ATTR patients. Diagnostic delay was higher in ATTR (2.8 ± 4.3 vs 0.6 ± 0.7 years, P < .001), but mortality was greater in AL patients (48% vs 32%, P = .028). Independent predictors of mortality were AL subtype (HR, 6.16; 95%CI, 1.56-24.30; P = .01), female sex (HR, 2.35; 95%CI,1.24-4.46; P = .01), and NYHA functional class III-IV (HR, 2.07; 95%CI, 1.11-3.89; P = .02).ConclusionsCA is a clinical challenge, with wide variability in its presentation depending on the subtype, leading to diagnostic delay and high mortality. Improvements are needed in the early diagnosis and treatment of these patients.     

How do we interpret an elevated carbohydrate antigen 19-9 level in asymptomatic subjects?

AimThis prospective cohort study aimed to evaluate the etiology of elevated CA 19-9 levels and to present appropriate guidelines for the asymptomatic patients.MethodsBetween January 2004 and March 2007, we enrolled consecutive asymptomatic patients who had elevated CA 19-9 levels >37 U/mL. To evaluate the etiology, the CA 19-9 level was rechecked and further studies were carried out. If the CA 19-9 level decreased to the normal range, or if it showed a decreasing trend, then it was monitored annually. Yet, if the CA 19-9 level showed an increasing trend, then the level was monitored at intervals of 1, 3, and 6 months until no evidence of malignancy was proven.ResultsOf the 62,976 patients, 501 (0.8%) subjects showed an elevated CA 19-9 level. This prospective analysis was conducted on 353 subjects (70.5%) who were followed up for at least 6 months. Ten patients (2.8%) were diagnosed with malignancies. There were 97 patients (27.5%) with benign diseases and 246 patients (69.7%) were deemed non-specific.ConclusionsCA 19-9 should not be used as a screening tool. In the case of a persistently elevated CA 19-9 level, further work-up for determining the etiology should be done.     

Efficacy and safety of recombinant growth hormone treatment in children with growth retardation related to long-term glucocorticosteroid therapy

ObjectiveTo evaluate safety and efficacy of recombinant human growth hormone treatment in children on long-term glucocorticoid therapy.MethodsA 5-year prospective open-label study included children on glucocorticoid therapy with either standard deviation score (SDS) < −2 for height for chronological age (CA) if naïve to growth hormone treatment, or annual growth rate ≥ 0 SDS for CA if currently receiving growth hormone.ResultsNinety-eight patients began treatment, 63 discontinued; 59 were analyzed for safety and 58 for efficacy. There was male predominance (78.0%). Median age was 13.0 years. Median height screening was 136.0 cm (range, 95.1–159.7 cm). Mean SDS for height for CA in the efficacy analysis set was −2.91 ± 1.19 (range, −7.49 to −0.96). Mean growth hormone dose was 0.4, 0.4, 0.4 and 0.3 mg/kg/week at month 0, M12, M24, and M36, respectively. Primary analysis of change in SDS for height for CA from baseline to M36 showed a significant increase of 0.80 ± 1.03. Twenty patients in the safety analysis set had ≥ 1 treatment-emergent adverse event (TEAE) related to study treatment. Two patients experienced serious treatment-related TEAEs: 1 case of poor compliance, and 1 of mild hyperglycemia, both already observed under growth hormone treatment.ConclusionThis study suggests that growth hormone treatment could be effective in increasing height in children on long-term glucocorticoid treatment with a safety profile comparable to that in approved rhGH treatment indications.Clinical trial registrationNCT00163189.     

Clinical utility of serum beta-2-microglobulin as a predictor of diabetic complications in patients with type 2 diabetes without renal impairment

AimAs serum beta-2-microglobulin (B2M) levels are usually elevated in patients with renal failure, they have been suggested as a surrogate marker of cardiovascular mortality for patients with chronic kidney disease. Glycation of B2M is cytotoxic and may contribute to the risk of diabetic complications in patients with diabetes. Our objective was to evaluate the relationship between B2M and diabetic complications in patients with type 2 diabetes (T2D) and normal kidney function.MethodsA total of 366 patients with T2D and preserved renal function with no clinical evidence of cardiovascular disease were enrolled consecutively into this study. High B2M was defined as a median serum B2M level ≥ 1.8 mg/L. Subclinical atherosclerosis was defined as a carotid artery intima–media thickness (C-IMT) ≥ 0.9 mm or the presence of carotid plaque. The definition of diabetic nephropathy was based on the presence of albuminuria (≥ 30 mg/g creatinine).ResultsPatients with high B2M were older, and had diabetes of longer duration, higher serum creatinine, microalbuminuria, and increased vascular stiffness and C-IMT compared with patients with low B2M. B2M levels were positively correlated with C-IMT and vascular stiffness, and these associations remained constant after adjusting for age. In addition, after adjusting for age, gender, body mass index, serum creatinine, hypertension, smoking and alcohol consumption, the adjusted odds ratio (OR) for atherosclerosis was 2.01 [95% confidence interval (CI): 1.02–3.94] per 1 mg/L increase in B2M. The prevalences of diabetic retinopathy and nephropathy were significantly higher with a high B2M than with a low B2M. The multiple adjusted OR for diabetic nephropathy was 2.29 (95% CI: 1.11–4.72) per 1 mg/L increase of B2M.ConclusionHigher serum B2M was an independent risk factor for subclinical atherosclerosis and diabetic nephropathy in patients with T2D without renal impairment.     

Coeliac autoimmunity in type I diabetes mellitus

Background and study aimsCoeliac autoimmunity (CA) has a known association with type 1 diabetes mellitus (T1DM) for which screening is routinely recommended but less frequently followed. The impact of CA in T1DM has been variably reported. The aims of this study are as follows: (1) to study the prevalence of CA in patients with T1DM and (2) to study the impact of CA not only on nutritional parameters but also on glycaemic control, endocrine axes and bone health.Patients and methodsEighty-six consecutive patients with T1DM were screened for CA using immunoglobulin A (IgA) tissue transglutaminase as a marker (TTG; IgG anti-gliadin in IgA-deficient case). CA positive (CA+) cases were compared with age-matched and sex-matched CA negative (CA−) T1DM cases for anthropometry, glycaemic control (assessed by glycated haemoglobin (HbA1c) and hypoglycaemic/hyperglycaemic episodes), endocrine (thyroid function, cortisol, growth hormone (GH) axis, gonadal axes), haematological (haemoglobin, iron profile and vitamin B₁₂ status) and calcium metabolism parameters and bone densitometry (by dual-energy X-ray absorptiometry (DXA)). Consenting patients with CA also underwent upper gastrointestinal (GI) endoscopy with duodenal biopsy.ResultsOut of 86 patients, 11 (12.75%) screened positive for CA (seven patients underwent duodenal biopsies which were suggestive of Marsh grade III(2), II(3) and I(2) disease). The CA+ T1DM patients were comparable with CA− T1DM in terms of anthropometry. CA+ patients had higher HbA1c (10.7 ± 1.8 vs. 8.4 ± 1.0 (93 ± 19 vs. 68 ± 11 mmol/mol); p < 0.01), more hypoglycaemic episodes (five vs. two; p < 0.05), higher prevalence of iron and vitamin B₁₂ deficiency, lower insulin-like growth factor-1 (IGF-1) levels and lower bone mineral density (BMD) z-score at total body (−1.91 ± 1.05 vs. −0.63 ± 0.73; p < 0.05) and lumbar spine (−1.69 ± 0.92 vs. −0.36 ± 0.93; p < 0.05). The incidence of fractures in the past 3 years was also more in CA+ patients than in CA− patients (four vs. one; p < 0.05).ConclusionCA has an important autoimmune association with T1DM. The concomitant presence of CA adversely affects stature, bone health, glycaemic control and iron and B₁₂ levels in T1DM. IgA sufficiency should be ensured before using an IgA-based screening test for CA.     

Circulating Bcl-2 concentrations and septic patient mortality

IntroductionThere are not data on blood B-cell lymphoma 2 (Bcl-2) concentrations (one of the antiapoptotic molecules of the Bcl-2 family in the intrinsic apoptosis pathway) in septic patients. Therefore, this study was carried with the aims to explore whether blood Bcl-2 concentrations at diagnosis of sepsis are different in survivor and non-survivor septic patients, are associated with mortality, and are useful for the mortality prediction.MethodsIntensive Care Units from 3 Spanish hospitals participated in this observational and prospective study with septic patients and serum Bcl-2 concentrations at diagnosis of sepsis were determined. Mortality at 30 days was as outcome variable.ResultsWe found that 30-day non-surviving patients (n = 81) showed lower serum Bcl-2 levels (p = 0.003) than surviving patients (n = 140). We found that serum concentrations of Bcl-2 < 4.4 ng/mL were associated with mortality (OR = 3.228; 95% CI = 1.406–7.415; p = 0.006) in the multiple logistic regression analysis, and that showed an area under the curve for mortality prediction of 62% (95% CI = 55–68%; p = 0.003).ConclusionsIn our study appears novel findings such as higher blood Bcl-2 concentrations in survivor than in non-survivor septic patients, the association between low blood Bcl-2 concentrations and mortality of septic patients, and the ability of blood Bcl-2 concentrations for the prediction of septic patient mortality.     

Sonographic features suggestive of amyloidosis in hemodialysis patients: Relations to serum beta2-microglobulin

Aim of the workTo determine sonographic features suggestive of amyloidosis in hemodialysis patients complaining of shoulder pain, and to study their relations to serum beta2-microglobulin (β2M).Patients and methodsClinical examination, skeletal survey, musculoskeletal ultrasonography of the shoulder joints, and serum β2M were done for 32 patients with end stage renal disease, who were regular on hemodialysis.ResultsSerum β2M levels were markedly raised in all patients, and increased with increasing duration of dialysis (r = 0.91, p < 0.001). Twenty-five patients had a non homogeneous thickening of the supraspinatus tendon >7 mm, and thickening of the biceps tendon >4 mm, 30 had synovial deposits, 27 had subdeltoid bursa effusion, 25 had thickened subacromial bursa, 7 had supraspinatus tendon tear, and 17 had bony erosions. Serum β2M levels significantly correlated with thickened supraspinatus tendon (>7 mm) and supraspinatus tendon tear (r = 0.41, p = 0.03 and r = 0.42, p = 0.01 respectively). Long time on hemodialysis was the significant independent determinant for supraspinatus tendon tear and humeral head erosions (p = 0.001 for each).ConclusionElevated serum β2M levels and sonographic features suggestive of dialysis-related amyloidosis (DRA) were found in all hemodialyzed patients complaining of shoulder pain either with or without clinical and/or radiological features suggestive of DRA. So, for diagnosis of DRA, sonographic features should correspond to the presence of clinically or radiologically evident β2M amyloid, and we should exclude other causes of non-amyloid changes.     

Variants within the calpain-10 gene and relationships with type 2 diabetes (T2DM) and T2DM-related traits among Tunisian Arabs

BackgroundCommon variations in the calpain 10 (CAPN10) gene variants UCSNP-43, UCSNP-19 and UCSNP-63, and the 112/121 diplotype, are associated with an increased risk of type 2 diabetes (T2DM) and T2DM-related traits.MethodsThe association of UCSNP-43, -19 and -63 CAPN10 SNPs with T2DM was assessed in 917 Tunisian T2DM patients and 748 ethnically matched non-diabetic controls. CAPN10 genotyping was done by PCR-RFLP.ResultsSignificant differences in UCSNP-19 MAF, but not UCSNP-43 or -63, and genotype distribution were seen between patients and controls. Heterogeneity in UCSNP-19, but not UCSNP-43 and -63, genotype distribution was noted according to geographical origin. Obesity was associated with UCSNP-19, while raised fasting glucose was associated with UCSNP-63, and increased HDL was associated with UCSNP-43. Enrichment of homozygous UCSNP-19 2/2 was seen in overweight and obese compared with lean patients; logistic-regression analyses demonstrated a positive association of the 2/2 genotype with overweight [P = 0.003; OR (95% CI) = 2.07 (1.28–3.33)] and obese [P = 0.021; OR (95% CI) = 1.83 (1.10–3.07)] patients. Of the six CAPN10 haplotypes identified, significant enrichment of only haplotype 111 was seen in T2DM patients [Pc = 0.034; OR (95% CI) = 1.22 (1.06–1.41)], while the frequency of all identified CAPN10 diplotypes, including the high-risk 112/121, was comparable between patients and controls.ConclusionWhile CAPN10 UCSNP-19 SNP and haplotype 111 contribute to the risk of T2DM in Tunisian subjects, no significant association between CAPN10 diplotypes and T2DM was demonstrated.     

Upper gastrointestinal involvement in paediatric onset Crohn's disease: Prevalence and clinical implications

Background and aimsOur study evaluated the prevalence, the characteristics and implications of the upper gastrointestinal localisation (UGI+) in paediatric Crohn's Disease (CD) patients.MethodsThis prospective study evaluated 45 newly diagnosed CD patients at diagnosis and follow up with respect to CD localisation.ResultsAll patients presented CD at the colon and/or ileum. In 24/45 patients (53.3%, 12 F and 12 M) an UGI+ involvement was also found. UGI+ patients had a younger age of onset (10.9 years versus 12.6 years; P < 0.05). PCDAI at diagnosis was significantly higher in the UGI+ (41 vs. 25 P < 0.01). UGI+ patients were overall more symptomatic. Pancolitis and extraintestinal manifestations were also more frequent (19/24 (80%) vs. 12/21 (57%) P < 0.01). Growth was more impaired at diagnosis in UGI+ patients. By the end of the follow-up (mean 3 years, range 2 to 4) no significant difference was found in PCDAI (17 in UGI+ patients vs. 11 in UGI− P = NS), or the number of relapses. Weight and growth catch-up in UGI+ patients were comparable to UGI− ones. However, UGI+ patients required a more aggressive therapeutic approach.ConclusionAt least half of paediatric onset CD patients have an upper gastrointestinal localisation. UGI+ patients present an earlier onset and a more severe disease. The final outcome does not differ, but UGI+ patients require a more aggressive therapeutic approach.     

Macrophage stimulating protein variation enhances the risk of sporadic extrahepatic cholangiocarcinoma

BackgroundPrimary sclerosing cholangitis confers risk of cholangiocarcinoma. Here, we assessed the primary sclerosing cholangitis-associated variant rs3197999 in the MST1 gene, coding for RON receptor tyrosine kinase ligand macrophage stimulating protein, in a large European cholangiocarcinoma cohort.Materials and methods223 cholangiocarcinoma patients including three primary sclerosing cholangitis individuals and 355 cancer- and primary sclerosing cholangitis-free controls were genotyped for MST1 rs3197999.ResultsThe cancer group departed from Hardy–Weinberg equilibrium (p = 0.022) and exhibited a trend for rs3197999 [A] overrepresentation (31% vs. 26%: p = 0.10). Homozygous rs3197999 [AA] carrier status significantly increased overall (OR = 1.97; p = 0.023) and primary sclerosing cholangitis-unrelated biliary tract cancer risk (OR = 1.84; p = 0.044), relative to homozygous common allele carriers. The association was most pronounced in patients with extrahepatic tumours. This finding was robust to multivariate analysis (p < 0.05), validating the [AA] genotype as an independent cholangiocarcinoma risk factor.ConclusionsThese results suggest that the [AA] genotype of the common MST1 variant rs3197999 enhances genetic risk of sporadic extrahepatic cholangiocarcinoma irrespective of primary sclerosing cholangitis status, presumably by modulating inflammatory responses and/or altered MSP/RON signalling.     

Outcome following Heart Transplantation in New Zealand Maori

BackgroundDisparities in health care access and outcomes between Maori (M) and Non-Maori (NM) New Zealanders have been reported but little is known about access to and outcomes following heart transplantation (HT).MethodsA retrospective analysis was performed of M and NM who underwent HT in New Zealand. Demographic, clinical and outcome data were collected.ResultsOf 253 patients transplanted, 176 were European, 47 M (19%) and 30 of other ethnicities. M and NM groups were compared. Median age (both 46 years), gender (17% vs 21% female), waiting time (90 vs 76 days) and diagnosis (dilated cardiomyopathy – 62% vs 58%) were similar for both groups. M were heavier (81 vs 71 kg, p < 0.0001) and more were blood group A (58% vs 39%). Five year survival was similar (79% vs 78%) but 10 year survival was significantly reduced in M (54% vs 67% p = 0.02).ConclusionThe proportion of Maori who have undergone heart transplantation in New Zealand compares favourably with their proportion in the New Zealand population. The reasons for the adverse diverging outcomes after five years require further investigation.     

Evolución de tubulopatías renales primarias diagnosticadas en edad pediátrica

Background and objectivePrimary tubulopathies are rare and usually present at pediatric age. Recent advances in genetic diagnosis and treatment have changed its natural history. This study provides the clinical spectrum of a series of primary tubulopathies diagnosed in a Pediatric Nephrology Unit and to offer long-term follow-up data regarding growth, estimated glomerular filtration and intercurrent complications.Patients and methodsObservational study in 53 patients with primary tubulopathies and identified genetic defect: Gitelman syndrome (36%), distal renal tubular acidosis (15%), cystinuria (11%), X-linked hypophosphatemic rickets (7%), Dent-syndrome Lowe (7%), cystinosis (6%), and 1-2 cases of other tubulopathies. Demographic, analytical and clinical data were collected at diagnosis, during evolution and at the time of the study.ResultsThe age (median and interquartile range) at diagnosis was 5.08 years (1.33-8.50). The most frequent presentation manifestations were metabolic decompensations associated with intercurrent processes (40%) and short stature (38%). Height (mean ± SD) was ?1.39 ± 1.49 at diagnosis and 1.07 ± 1.54 after a follow-up of 18.92 (6.25-24.33) years. Sixteen (32%) developed an estimated glomerular filtration < 90 ml / min / 1.73 m². Three patients required replacement renal replacement. Eleven patients had metabolic decompensations that required hospitalization, 9 renal colic and / or kidney stones and 10 mental problems. Six of 8 patients with distal renal tubular acidosis developed sensorineural deafness.ConclusionsPrimary tubulopathies are a heterogeneous group of diseases that cause growth impairment, largely reversible with treatment, risk of estimated glomerular filtration reduction and significant extrarenal complications derived or associated.     

Hypoalbuminemia and Lymphocytopenia in Patients With Decompensated Biventricular Failure

BackgroundIn patients hospitalized with decompensated biventricular failure having hypoalbuminemia and lymphocytopenia without underlying hepatic or renal disease, we addressed the presence of a protein-losing enteropathy (PLE).MethodsWe studied 78 patients having a dilated cardiomyopathy, who were hospitalized with congestive heart failure (CHF) and hypoalbuminemia of uncertain origin. In the first 19 patients, we investigated the presence of PLE using Tc-Dex⁷⁰ scintigraphy together with serum albumin 2 to 4 weeks later when compensation had been restored. In the next 59 patients, presenting with reduced serum albumin and relative lymphocyte count at admission, these parameters were again monitored (2–4 weeks) later when symptoms and signs of CHF had resolved.ResultsPLE, documented by Tc-Dex⁷⁰ scintigraphy, was found in 10 of 19 patients and whose hypoalbuminemia (2.7 ± 0.1 g/dL, mean ± standard error of mean) were corrected (3.3 ± 0.1 g/dL; P < 0.05) with the resolution of CHF, whereas in the 9 patients without a PLE, reduced baseline serum albumin (2.6 ± 0.1 g/dL) failed to improve on follow-up (2.6 ± 0.2 g/dL) in keeping with malnutrition. Relative lymphocyte count was reduced (14.6 ± 1.5%) in patients with PLE but was normal (21.4 ± 3.3%; P < 0.05) in those without PLE. Serum albumin and relative lymphocyte count were each reduced at admission (2.8 ± 0.1 g/dL and 14.4 ± 1.0%, respectively) in 59 patients and increased (P < 0.05) to normal values (3.5 ± 0.1 g/dL and 24.9 ± 1.0%) 2 to 4 weeks after they were compensated.ConclusionsEnteral losses of albumin and lymphocytes account for the reversible hypoalbuminemia and lymphocytopenia found in patients hospitalized with CHF having splanchnic congestion.     

Niveles séricos de inmunoglobulinas,componentes 3 y 4 del complemento,alelo HLA-B27 y espondiloartropatía en pacientes con uveítis anterior no infecciosa

ObjectiveTo identify the relationship between serum immunoglobulin levels, complement components 3 and 4, the presence of the HLA-B27 allele and diagnosis of spondyloarthropathies in patients with non-infectious anterior uveitis.Materials and methodsThe participants were 197 patients with a non-infectious anterior uveitis. The concentrations of serum immunoglobulins, and C3 and C4 proteins of the complement were determined by turbidimetry. The personal history of suspected immunodeficiency, ophthalmological complications, arthralgia, family history of spondyloarthropathies and the presence of the HLA-B27 allele were collected.ResultsA family history of spondyloarthropathy, axial arthralgias, and ophthalmological complications were more frequent in HLA-B27 positive patients (P = .0005, P ≤ .0001, and P ≤ .0001, respectively) and in patients with spondyloarthropathy diagnoses (P ≤ .0001, P ≤ .0001, and P ≤ .0001, respectively). A personal history of recurrent sepsis, and gastrointestinal abnormalities was associated with the presence of the HLA-B27 allele (P ≤ .0001, and P = .0240, respectively) and with the diagnosis of spondyloarthropathy (P = .0492, and P = .0017, respectively). IgG decrease was observed (χ2 = 18.5, OR 5.03, 95% CI 2.32-10.89; P = .0001) and IgM (OR 7.13, 95% CI 1.40-36.4; P = .0128) in patients positive for the HLA-B27 allele and in patients with a diagnosis of spondyloarthropathies (P = .0364 and P = .0028, respectively). The decrease of C3 proteins (OR 4.82; CI 95% 1.35-17.11; P = .0328) and C4 (OR 9.09; CI 95% 2.13-38.88; P = .0074) were associated with a spondyloarthropathies diagnosis.ConclusionsPatients with non-infectious anterior uveitis, positive for the HLA-B27 allele and diagnosed with spondyloarthropathies have alterations in serum immunoglobulin levels and complement components 3 and 4, which could contribute to the perpetuation and worse clinical course of this disease.     

Surgical Treatment and Prognostic Analysis of 93 Cases of Hilar Cholangiocarcinoma

ObjectiveTo explore the surgical treatment and prognosis of hilar cholangiocarcinoma.MethodsThis was a retrospective study of 93 cases of hilar cholangiocarcinoma that were treated surgically at our hospital from June 1999 to June 2005. Prognostic factors were also analyzed.ResultsFifty-two cases were treated with curative resection, 21 with palliative resection, and 9 with nonoperative drainage. Eleven cases underwent palliative drainage operations. The median survive time was 31 months in the curative resection group, 13.7 months in the palliative resection group, and 11 months in the nonoperative drainage group. Patient age, serum total bilirubin, clinical type of Bismuth-Corlette, tumor differentiation, and lymph node metastases were important factors for predicting the prognosis of hilar cholangiocarcinoma.ConclusionsResection was the main treatment for hilar cholangiocarcinoma, and curative resection was the best way to obtain better prognosis. Age, preoperative serum total bilirubin, bismuth clinical type, tumor histopathological grading, and lymph node metastases were considered to have a significant effect on prognosis.     

Diagnostic value of dobutamine stress Doppler tissue imaging in diabetic patients with suspected coronary artery disease

BackgroundCoronary artery disease (CAD) is often silent in diabetic patients, and it is typically in advanced stages of development by the time it manifests. Various forms of stress testing have been investigated to detect obstructive CAD in diabetes mellitus.ObjectivesTo assess the diagnostic value of dobutamine stress pulsed-wave Doppler tissue imaging (DTI) compared with standard wall motion analysis in detection of myocardial ischemia in diabetic patients with suspected CAD.MethodsThe study comprised 46 diabetic patients with suspected CAD who underwent dobutamine stress echocardiography (DSE) with DTI within 4 weeks before coronary angiography (CA). Dobutamine infusion started at 5 μ/kg/min and increased up to 40 μ/kg/min with additional atropine during submaximal heart rate responses. In addition to wall-motion score index (WMSI) analysis, pulsed-wave DTI examination of basal and mid segments of posteroseptal, lateral, anterior, inferior and anteroseptal walls was performed. Myocardial velocities were measured at rest in the apical 4, 3 and 2-chamber views. The measurements were repeated at low dose (10–15 μ/kg/min) and at peak stress (40 μ/kg/min). DTI measurements included peak systolic velocity (S), peak early diastolic velocity (E) and peak late diastolic velocity (A) and the results were compared to WMSI analysis. Patients were classified into two groups according to CA results; group (I) diabetics with positive CA (n = 27) and group (II) diabetics with negative CA (n = 19).ResultsThere was no significant difference between the two groups in duration of diabetes, global WMSI at rest or the Δ changes (stress-rest/rest) of WMSI (p > .05). Global S and global E were significantly lower in group I compared to group II at peak stress (11.3 ± 3.7 cm/s vs. 14.5 ± 2.2 cm/s, p < 0.01) and (11.3 ± 1.6 cm/s vs. 13.1 ± 2.1 cm/s, p < 0.01) respectively. The cutoff points for global S and global E to detect obstructive CAD in diabetics were 11.3 cm/s and 11.2 cm/s respectively with 75.7%, 73.4% sensitivity and 94.7%, 89.47% specificity respectively. An increment (Δ changes) less than 0.56 in S or 0.26 in E from rest to peak stress identified CAD with 78.8%, 89.3% sensitivity and 94.7%, 90.7% specificity respectively. The accuracy of DTI parameters during peak stress was higher than WMSI analysis (sensitivity 74.1% vs. 59.3% and specificity 90% vs. 79%, p < 0.01 for each). In multivariate regression analysis, only ΔS and ΔE were independent predictors of obstructive CAD in diabetics (odd ratio: 36.16, 95% CI, 1.34–532.01 and 63.77, 95% CI, 3.19–721.47) respectively.ConclusionQuantitative analysis, using DTI during DSE, adds new dimension in diagnosis of myocardial ischemia. It is more sensitive, specific, accurate and reproducible compared with standard wall motion analysis for recognition of significant CAD in diabetic patients.