Descriptive study of naevus involution in a series of 74 patients with atypical naevus syndrome under SIAscopy digital follow-up.

BACKGROUND: Characterization of nevi involution could help to understand the biological behaviour of melanocytic neoplasms. OBJECTIVE: To describe the frequency and morphology of naevus involution in a series of patients with atypical naevus syndrome under digital follow-up with a SIAscopy program and, in a small sample of fading nevi, to analyse histopathological features and immunohistochemical biomarkers. METHODS: Seventy-four patients registered from April 2007 to July 2014 in the SIAscopy system of the Department of Dermatology of Hospital Arnau de Vilanova of Lleida, Spain, were reviewed. Fourteen naevus cases with fading features were prospectively excised during follow-up. Eleven already excised naevus controls were randomly selected from our archive. RESULTS: We observed that 81% of patients showed, at least, one involutive naevus and 25% of recorded nevi presented this phenomenon; the mean time of involution was 46.7 months. The predominant structural pattern was reticular (>70%), and the most frequently observed regression structures were vascular (33.8%). Histopathological significant higher intensity of inflammatory infiltrate in controls and higher presence of laminar and compact fibrosis and increase of vessels in cases were demonstrated. Regarding immunohistochemical biomarkers, only higher expression of cytoplasmic activated caspase 3 in controls was significant. CONCLUSIONS: Naevus involution is a common phenomenon in patients with dysplastic naevus syndrome. It is usually a slow process, more frequent in naevus with reticular pattern. SIAscopy regression structures are uncommon, with the exception of vascular ones. Histologically, fading involutive pattern is characterized by scarce inflammatory infiltrate and melanophages, delicate fibrosis and increase of vessels.

Immunohistochemical analysis of T-type calcium channels in acquired melanocytic naevi and melanoma.

BACKGROUND: Cutaneous malignant melanoma arises from transformed melanocytes de novo or from congenital or acquired melanocytic naevi. We have recently reported that T-type Ca2+ channels (TT-Cs) are upregulated in human melanoma and play an important role in cell proliferation. OBJECTIVES: To describe for the first time in formalin-fixed paraffin-embedded tissue the immunoexpression of TT-Cs in biopsies of normal skin, acquired melanocytic naevi and melanoma, in order to evaluate their role in melanomagenesis and/or tumour progression, their utility as prognostic markers and their possible use in targeted therapies. METHODS: Tissue samples from normal skin, melanocytic naevi and melanoma were subjected to immunohistochemistry for two TT-Cs (Cav3.1, Cav3.2); markers of proliferation (Ki67), the cell cycle (cyclin D1), hypoxia (Glut1), vascularization (CD31) and autophagy (LC3); BRAF V600E mutation (VE1) and phosphatase and tensin homologue (PTEN). Immunostaining was evaluated by histoscore. In silico analysis was used to assess the prognostic value of TT-C overexpression. RESULTS: TT-C immunoexpression increased gradually from normal skin to common naevi, dysplastic naevi and melanoma samples, but with differences in the distribution of both isoforms. Particularly, Cav3.2 expression was significantly higher in metastatic melanoma than in primary melanoma. Statistical correlation showed a linear interaction between PTEN loss/BRAF V600E/Cav3.1/LC3/ Ki67/cyclin D1/Cav3.2/Glut1. Disease-free survival (DFS) and overall survival correlated inversely with overexpression of Cav3.2. DFS also correlated inversely with overexpression of Cav3.1. CONCLUSIONS: TT-C immunoexpression on melanocytic neoplasms is consistent with our previous in vitro studies and appears to be related to tumour progression. TT-C upregulation can be considered as a prognostic marker using The Cancer Genome Atlas database. The high expression of Cav3.2 in metastatic melanoma encourages the investigation of the use of TT-C blockers in targeted therapies.

[Long-term evaluation of immune response to hepatitis B vaccine in 136 patients undergoing hemodialysis]. / Evaluación a largo plazo de la respuesta inmunológica a la vacuna de la hepatitis B en 136 pacientes en hemodiálisis.

UNLABELLED: Hemodialysis (HD) patients have an impaired response to hepatitis B(HB) vaccines, and the persistence of immunity, the efficacy of revaccination and the periodicity of post-vaccination testing are not well defined. We present the experience during 13 years in an outpatient dialysis center of 136 HD patients who completed a HB vaccination program consisting in 3 doses of 40 microg intramuscular recombinant B vaccine (Engerix-B). In all patients anti-HBs titers were determined annually and in 31 patients every 6 months. Nonresponders patients and responders patients that lost their antibodies(< 10 UI/ml) received annually a booster double dose of vaccine. Seventy-four patients(54.4%) developed immunity and the remaining 62 patients were considered nonresponders. When compared both groups, gender and the etiology of chronic kidney disease did not differ between the two groups; nevertheless, nonresponders patients were significantly older than responders. After 1 year of follow-up, 32% of responders had no detectable anti-HBs levels, and only 18% of patients remained immunoreactive 6 years afer vaccination. The peak anti-HBs titer immediately after completion of the vaccination schedule was found to be a major predictor of maintaining immunity: 75% of patients with anti-HBs titers greater than 1000 IU/ml remained immunoreactive 3 years after vaccination compared to 47% of patients with titers between 100-999 IU/ml(p=0.08) and 34% of patients with titers between 11-99 IU/ml(p=0.02). The administration of additional doses of vaccine were effective in 24% of the nonresponders patients, and 69% of them remained seropositive at the end of the 1-year follow up. Repeated booster doses of vaccine in nonresponders patients to the first booster dose afforded seroconversion in 19.6% of the patients. Performing post-vaccination testing every six months it would have allowed to give booster doses of vaccine in 16% of responder patients before the annual period. CONCLUSION: This current study demonstrates that a HB vaccination schedule with a regular serological follow-up and repeated booster doses , affords an acceptable seroprotection in HD patients.

[Is there a relationship between cystatin C and inflammatory status, oxidative stress and other cardiovascular risk factors in non-diabetic patients with chronic kidney disease?]. / ¿Existe relación entre los niveles de cistatina C y el estado inflamatorio, el estrés oxidativo y otros factores de riesgo cardiovascular en pacientes no diabéticos con enfermedad renal crónica?

UNLABELLED: Cystatin C is a marker of renal function and a major cardiovascular risk factor. In the general population, cystatin C appears to be influenced by factors other than renal function alone. However, information for serum cystatin C levels in chronic kidney disease (CKD) is lacking. METHODS: We studied 52 nondiabetic patients (38 men, mean age 49 years) with CKD stage 3 (22), 4 (25) or 5 (5) who had measurements of serum cystatin C levels, estimated glomerular filtration rate (MDRD), inflammatory (C-reactive protein, interleukin-6 and fibrinogen), and oxidative markers (anti-oxidized LDL antibodies, serum paraoxonase-1 activity and concentration), left ventricular mass index by echocardiography and other cardiovascular risk factors. RESULTS: Mean cystatin C levels were 2.35 +/- 0.9 mg/l. Cystatin C was positively correlated with creatinine serum levels, estimated glomerular filtration rate, PTH levels and negatively with anti-oxidized LDL antibodies. On the other hand, cystatin C was not related to inflammatory markers, serum paraoxonase-1 activity and concentration, proteinuria, HDL or LDL cholesterol, serum triglycerides, left ventricular mass index or demographic factors such as age, body mass index and blood pressure. After adjustment for PTH levels and anti- oxidized LDL antibodies, only estimated glomerular filtration rate was independently related serum cystatin C levels (beta = -0.500, p = 0.001). CONCLUSION: In nondiabetic patients with CKD, cystatin C is closely related to the degree of renal dysfunction. In contrast, inflammatory state, oxidative stress, left ventricular mass index and other cardiovascular risk factors are not related to cystatin C levels in this population.

Left ventricular mass and diastolic function in normotensive young adults with autosomal dominant polycystic kidney disease.

Left ventricular hypertrophy is often found very early in the course of autosomal dominant polycystic kidney disease (ADPKD). Diastolic dysfunction has been shown in hypertensive adult patients with ADPKD with increased left ventricular mass (LVM), but there are no data about diastolic function in the young ADPKD population without hypertension and with normal renal function. To evaluate very early alterations in cardiac structure and diastolic function in young normotensive patients with ADPKD, color Doppler echocardiography was performed in 46 young normotensive patients with ADPKD and 35 healthy subjects. LVM, transmitral pulsed Doppler flow (diastolic function), and valvular abnormalities were studied. Patients with ADPKD showed higher LVM indices (LVMIs) than controls (89.7+/-17.3 v 68.5+/-17.2 g/m2; P < 0.0001). Peak early diastolic velocity (E wave) deceleration time and isovolumic relaxation time were significantly prolonged in patients with ADPKD compared with controls (E wave deceleration time, 182.5+/-51.3 v 149.4+/-34 msec; P=0.002; isovolumic relaxation time, 97.7+/-17.5 v 79+/-15 msec; P=0.0001). No differences were found in valvular abnormalities in the two groups. In conclusion, young normotensive patients with ADPKD showed increased LVMIs and Doppler abnormalities consistent with early diastolic dysfunction.

Pseudotumor cerebri: an unusual complication of brachiocephalic vein thrombosis associated with hemodialysis catheters.

We report a case of pseudotumor cerebri (PC) in a maintenance hemodialysis patient that was associated with thrombosis of the right and left brachiocephalic veins caused by repeated subclavian and jugular vein catheterizations. Symptoms and signs of PC appeared when a right forearm Gortex graft was inserted. PC secondary to intracranial venous outflow obstruction is an important diagnostic consideration for hemodialysis patients with headache, visual disturbance, and papilledema.

Echocardiographic evaluation in patients with autosomal dominant polycystic kidney disease and end-stage renal disease.

Cardiovascular abnormalities have been considered important extrarenal manifestations of autosomal dominant polycystic kidney disease (ADPKD). However, little is known about their prevalence in patients with ADPKD undergoing hemodialysis (HD). To investigate whether cardiac abnormalities are more prevalent in these patients, clinical and echocardiographic manifestations of cardiovascular disease were evaluated in a group of 32 patients with ADPKD and a matched control group of 32 patients without diabetes treated by chronic HD for more than 6 months. Predialysis systolic and diastolic blood pressure (BP), prevalence of hypertension, and number of patients requiring antihypertensive medications were lower in the ADPKD group than controls. There was no difference in the prevalence of cardiac events, including cardiac failure, ischemic heart disease, and arrhythmia. Systolic dysfunction, diastolic patterns, and left ventricular hypertrophy were similar in the two groups. In patients with ADPKD, simple regression analysis showed left ventricular mass (LVM) index was correlated with hemoglobin level and predialytic systolic and diastolic BPs. In multiple regression analysis, predialysis systolic BP was the only independent variable linked to LVM index. The prevalence of aortic, mitral, and tricuspid valve disease did not differ between groups. In conclusion, the occurrence of cardiovascular complications in patients with ADPKD is similar to that of HD patients with other primary renal diseases, although hypertension is less prevalent.

Low risk of contrast nephropathy in high-risk patients undergoing spiral computed tomography angiography with the contrast medium iopromide and prophylactic oral hydratation.

BACKGROUND: Spiral computed tomography angiography (CTA) is a sensitive and specific technique for visualizing renal arteries and diagnosing renal artery stenosis (RAS). Whether spiral CTA is associated with increased risk of contrast nephropathy (CN) in patients with impaired renal function is unknown. METHODS: We prospectively studied 50 patients with chronic renal insufficiency (serum creatinine concentration greater than 1.58 mg/dl) who underwent spiral CTA with iopromide, a nonionic, low-osmolar contrast agent. Fourteen patients had diabetes mellitus. Patients were encouraged to drink 1 l of water 12 hours before and 2 l over 24 hours after the procedure. The presence of CN was defined by an increase of 20% or more in the baseline serum creatinine level within or 72 hours after administration of the radio-contrast agent. RESULTS: In the entire group, mean serum creatinine levels increased significantly from 2.92 +/- 1.39 to 3.06 +/- 1.55 mg/dl (p = 0.02) and mean creatinine clearance decreased from 29.8 +/- 12.9 to 28.9 +/- 12.8 ml/min (p = 0.009) 72 h after administration of the contrast medium. Two patients experienced an increase in serum creatinine level of 20%. Renal function returned to baseline within seven days in the 2 patients. Absolute changes in creatinine clearance after the administration of radiocontrast medium were similar in nondiabetic and diabetic patients and in the subgroup of patients, with a baseline serum creatinine of < 3 mg/dl and > or = 3 mg/dl. CONCLUSIONS: In patients with chronic renal insufficiency, spiral CTA performed with iopromide, a nonionic, low-osmolar contrast medium and a prophylactic oral hydratation, is a minimally invasive technique with low risk of contrast nephropathy.

Cardiac involvement in autosomal-dominant polycystic kidney disease: a hypertensive heart disease.

BACKGROUND: There is little information regarding the occurrence and distribution of cardiovascular abnormalities during the course of autosomal-dominant polycystic kidney disease (ADPKD). We conducted a cross-sectional study in three different groups of ADPKD patients to determine the profile and prevalence of cardiac involvement in this population. METHODS: Doppler color echocardiography was performed in 130 ADPKD patients. Patients were divided into normotensive (Group I, n=60), hypertensive (Group II, n=32) and those undergoing hemodialysis (Group III, n=38). RESULTS: There was a progressive increase in left ventricular mass (LVM) index (88.6+/-19.7, 127.6+/-40.4 and 150.5+/-56.5 g/m2, p < 0.0001) and in the prevalence of left ventricular hypertrophy (LVH) (3%, 43%, 62%, p < 0.0001) in Groups I, II and III, respectively. E/A ratio < 1 was found in 2% of normotensives, 46% of hypertensives and 62% of hemodialysis patients (p < 0.0001). Prevalence ofmitral valve prolapse and aortic and/or mitral regurgitation was 4.3% and 8.6%, respectively, in non-dialysis patients. The majority of valvular abnormalities occurred in dialysis patients, and were generally related to annular mitral calcification (28%) or aortic valve calcification (38%). Age, sex, systolic blood pressure (BP) and hemoglobin were independent predictors of LVM index in the entire population, systolic BP and creatinine in non-dialysis patients and systolic BP in dialysis patients. Age, heart rate and diastolic BP in the entire group, and age, heart rate and LVM index in non-dialysis patients remained as independent predictors of abnormal diastolic function. CONCLUSIONS: Cardiac involvement in ADPKD patients is a continuous process that evolves during the course of this disease. It is characterized by a low prevalence of specific valvular abnormalities, a progressive increase in LVM, LVH, and diastolic dysfunction, which are greatest in the latter stages of the disease. This study confirms the major influence of BP on cardiovascular abnormalities of ADPKD patients.

[Polymorphism of the renin-angiotensin system and renal failure]. / Polimorfismos del sistema renina-angiotensina e insuficiencia renal.

The renin-angiotenin-aldosterone system (RAAS) is not only involved in cardiovascular disease but also in renal pathophysiology and progression of renal disease. Several polymorphisms of genes coding for components of the RAAS have been identified. The I/D polymorphism of the ACE gene, a variant of the angiotensiogen gen, the M235T polymorphism, and the variant A1166 C polymorphism of the angiotensin II type 1 receptor gene are the most important. Several studies have suggested a potential role for I/D polymorphism of the ACE gen in the progression of renal diseases and in the cardiovascular death rate of patients with renal failure. Data on RAAS polymorphisms as determinants of the prevalence of renal diseases and the response to renoprotective therapies are conflicting. Given the polygenic nature of renal and cardiovascular disease and the growing number of candidate genes, large prospective and collaborative studies are required to assess the effect of RAAS polymorphisms on the progression of renal disease and on the response to renoprotective therapies.

[Hepatic involvement in boutonneuse fever (author's transl)]. / La afección hepática en la fiebre botonosa.

Boutonneuse fever is a rickettsioses which is endemic in the Mediterranean countries. Since 1972 we have had the chance to study eight observations os this disease (6 in the last year) and our attention has been drawn by the constant hepatic involvement. This was biological in all cases and histopathologic in the five patients submitted to a liver biopsy. Functional liver tests showed an elevation of SGOT and SGPT in six patients, as well as of the alkaline phosphatase and/or gamma-GT in five. No signs of hepatocellular insufficiency were detected and posterior controls demonstrated a complete normalization of the analytical parameters. As regards the histopathologic findings the most important was the fibrous enlargement of the porta spaces with slight infiltration by round cells, hyperplasia of the Kupffer's cells, and accumulations of histiocytes and lymphocytes. In no patient did we observed epithelioid granulomas. The authors conclude that the hepatic involvement in boutonneuse fever is benign but very constant, which means that it ought to be known about and that it has no defined histopathologic patterns.

[Oliguric and non-oliguric renal failure in high risk patient in intensive care units (author's transl)]. / Insuficiencia renal aguda oligúrica y no oligúrica en enfermos de alto riesgo ingresados en unidades de cuidados intensivos.

Oliguric and non-oliguric acute renal failure was studied in a group of 28 high risk patients in an intensive care unit. Of these, 15 (53.5%) presented oliguric and 13 (46.4%) non oliguric acute renal failure. Causal agents of the renal failure were postoperative in 14 cases, mainly peritonitis; medical in 10 and posttraumatic in 4. Oliguric renal failure was most commonly medical, while non-oliguric renal failure was predominantly postoperative in origin (p less than 0.05). Results of urinalysis indicative of renal failure were similar in both groups: NAO, osmolarity, FeNa, BUN o/p and creatinine o/p, as were degree and course of renal failure, and the appearance of complications and indications for dialysis. There was no significant difference in mortality rate between oliguric (93%) and non-oliguric (85%) patients; total mortality was 89%. The results of this study clearly show that non-oliguric acute renal failure carries the same poor prognosis in high risk patients in intensive care units as do the oliguric forms of the entity.

[Acute appendicitis in the elderly (author's transl)]. / Apendicitis aguda en el viejo.

The mortality rate and clinical, analytical, radiographic and pathologic data from 31 patients with acute appendicitis over 60 years of age are compared to those from 100 patients under 60. The elderly group showed a greater delay in medical consulting, a more diffuse abdominal pain and a greater incidence of perforated and gangrenous appendicitis. This last fact could be related not only to the consulting delay, but also to the own characteristics of the aged appendix. There were no significant differences between both groups regarding analytical results and radiographic findings. Mortality rate was 13 percent in the elderly, while it was null in the younger series.

[Acute abdomen in the elderly: etiology, complications, and prognosis. A review of 100 cases (author's transl)]. / Abdomen agudo en el viejo: etiología, complicaciones y pronóstico. A propósito de 100 casos.

One hundred cases of acute abdomen in patients over 70 years of age were studied. Mechanical occlusion was the most common cause among these patients, as opposed to acute appendicitis, which is the primary cause of the same condition among young people and adults. Irreducible hernias and visceral neoplasias were the most frequent etiologies among cases of mechanical occlusion. Cholecystitis took second place in our series. Visceral peforations were more often due to localized infections or visceral neoplasias than to gastric or duodenal ulcers. Overall mortality among these patients was 29 percent. Patients with visceral perforations due to localized infections or visceral neoplasias and all of the patients with vascular diseases had a negative prognosis.