Pregnancy in uremic patients: an eventful journey

Renal damage, which can be caused by gestational anomalies such as pre-eclampsia, carries a risk of gestational complications; the greatest risk being in women who become pregnant while on hemodialysis or peritoneal dialysis. If this rare event occurs, there is a marked increase in the risk of pre-eclampsia, early uterine contractions and hydramnios, hypertensive crisis, preterm delivery and intrauterine growth retard. Furthermore, newborns are almost always of low birthweight. Patients who undergo renal transplantation are another high-risk category. In such cases, the pregnancy itself can compromise the success of the transplant and the immunosuppressive therapy correlated to it can become a threat to the course of the pregnancy and normal fetal growth. Therefore, in view of the lack of appropriate guidelines for the best possible approach to the treatment of women on dialysis or of those with a renal transplantation, it is best to advise these patients against becoming pregnant and/or to provide a valid counselling service illustrating the extreme difficulties and dangers involved in becoming pregnant.     

BOOST: a phase 3 trial of sorafenib vs. best supportive care in first line treatment of hepatocellular carcinoma in patients with deteriorated liver function

Aim: Only patients with good liver function {[Child-Pugh (CP)] A class} were eligible for trials testing sorafenib as first-line treatment of hepatocellular car...     

Daily nutrient intake represents a modifiable determinant of nutritional status in chronic haemodialysis patients.

BACKGROUND: In maintenance haemodialysis patients, daily food intake is changeable; however, its relationship with nutritional status is unexplored. This study aimed to evaluate the isolated, long-term effect of daily nutrient intake on nutritional status in haemodialysis patients. METHODS: We performed a prospective 1-year controlled study in 27 chronic haemodialysis patients, without recognized risk factors for malnutrition. Each day for 1 week, four times in the year, we measured protein nitrogen appearance, and assessed dietary protein (DPI) and energy (DEI) intake from dietary diaries. We compared the nutritional outcome of patients spontaneously reducing nutrient intake below the threshold of 0.8 g/kg body weight/day for DPI and 25 kcal/kg body weight/day for DEI during the week (LOW, n = 8), with controls at adequate nutrient intake (CON, n = 19). An interventional 6-month study was then carried out in LOW to verify the cause-effect relationship. RESULTS: All patients showed a day-by-day reduction of whole nutrient intake during interdialytic period, which was mostly relevant in the third interdialytic day (L3). During the 1-year study, even in the presence of adequate dialysis dose and normal inflammatory indexes, body weight (68.0 +/- 5.5 to 65.8 +/- 5.9 kg), serum albumin (3.96 +/- 0.07 to 3.66 +/- 0.06 g/dl) and creatinine (9.2 +/- 1.1 to 8.1 +/- 0.7 mg/dl) significantly decreased in LOW but not in CON. Diaries evidenced in LOW a reduced number of meals at L3 that was explained by the fear of excessive interdialytic weight gain. During the interventional study, daily DPI and DEI increased at L3; this was associated with a significant increment of body weight, and serum albumin and creatinine levels. CONCLUSIONS: In maintenance haemodialysis patients the persistent, marked reduction of daily nutrient intake, even if limited to a single day of the week, is an independent determinant of reversible impairment of nutritional status.     

Video-Assisted Thyroidectomy Significantly Reduces the Risk of Early Postthyroidectomy Voice and Swallowing Symptoms

Background Voice and swallowing symptoms are frequently reported after thyroidectomy even in absence of objective voice alterations. We evaluated the influence of the video-assisted approach on voice and swallowing outcome of thyroidectomy. Methods Sixty-five patients undergoing total thyroidectomy (TT) were recruited. Eligibility criteria were: nodule size ≤30 mm, thyroid volume ≤30 ml, no previous neck surgery. Exclusion criteria were: younger than aged 18 years and older than aged 75 years, vocal fold paralysis, history of voice, laryngeal or pulmonary diseases, malignancy other than papillary thyroid carcinoma. Patients were randomized for video-assisted (VAT) or conventional (CT) thyroidectomy. Videostrobolaryngoscopy (VSL), acoustic voice analysis (AVA), and maximum phonation time (MPT) evaluation were performed preoperatively and 3 months after TT. Subjective evaluation of voice (voice impairment score = VIS) and swallowing (swallowing impairment score = SIS) were obtained preoperatively, 1 week, 1 month, and 3 months after TT. Results Fifty-three patients completed the postoperative evaluation: 29 in the VAT group, and 24 in the CT group. No laryngeal nerves injury was shown at postoperative VSL. Mean postoperative MPT, F ₀, F _low, F _high, and the number of semitones were significantly reduced in the CT group but not in the VAT group. Mean VIS 3 months after surgery was significantly higher than preoperatively in CT group but not in the VAT group. Mean SIS was significantly decreased 1 and 3 months after VAT but not after CT. Conclusions The incidence and the severity of early voice and swallowing postthyroidectomy symptoms are significantly reduced in patients who undergo VAT compared with conventional surgery. Presented at the ISW2007—IAES free paper session, Montreal, Canada, August 26–30, 2007.     

Nonfatal cerebral air embolism after dental surgery

After removal of four impacted third molars under general anesthesia, our patient developed subcutaneous emphysema, pneumothorax, pneumopericardium, and pneumomediastinum. Soon thereafter, coma with generalized epileptic status ensued. A cerebral magnetic resonance and single photon emission computed tomography showed hypoperfusion of the right thalamus and parietal, temporal, and frontal cortices. The likely mechanism was injection of air by the high-speed dental drill through the soft tissue adjacent to the roots of the lower molars. We were unable to find any previous report of systemic air embolism after oral surgery.     

Oxidative stress, inflammation and cardiovascular disease in chronic renal failure

Traditional risk factors such as hypertension, diabetes, dyslipidemia, obesity and metabolic syndrome, as well as additional nontraditional risk factors, can damage the kidney directly and by promoting intrarenal atherogenesis. Evidence indicates that increased oxidative stress and inflammation may mediate most of the effects of risk factors on the kidney. Clinical studies have demonstrated a relationship between oxidative stress and inflammatory biomarkers, and a few studies indicate an inverse correlation of oxidative stress biomarkers with estimated glomerular filtration rate (eGFR). Further, surrogate indexes of atherosclerosis such as intima-media thickness and aortic pulse wave velocity have been demonstrated to be related to plasma concentrations of markers of endothelial activation, inflammation and fibrosis in patients with different stages of chronic kidney disease (CKD). Moreover, plasma concentrations of high-sensitivity C-reactive protein have been shown to be increased and related to left ventricular mass in CKD individuals having left ventricular hypertrophy. In contrast, in these patients, decreases in fetuin-A plasma levels have been reported. Considering the complex background of the pathophysiological changes characterizing CKD patients, we can consider cardiovascular disease a multifactorial complication of CKD.     

Elevated levels of HER-2/neu and androgen receptor in clinically localized prostate cancer identifies metastatic potential

BACKGROUND: In this study, we investigated the expression of HER-2/neu and AR in clinically organ-confined prostate cancer to determine whether alterations in these signaling pathways contribute to the development of metastatic disease. METHODS: HER-2/neu and AR immunoreactivity were evaluated in archived prostatic tissues obtained from 53 men with clinically organ-confined disease who underwent radical prostatectomy. Associations between AR and HER-2/neu immunostaining and disease outcome were determined. RESULTS: Seventy percent (37/53) of tumors exhibited high levels of HER-2/neu immunostaining and 68% (36/53) of tumors had elevated AR levels. Patients with high levels of both HER-2/neu and AR had the highest rate of PSA failure (56%, 15/27) compared with no PSA failures amongst seven patients with low levels of both HER-2/neu and AR (log rank statistic 7.69, P = 0.021). Concurrent high levels of HER-2/neu and AR expression were significantly associated with high pathological stage (P = 0.027) and development of metastatic disease (P = 0.022). CONCLUSIONS: These findings support the notion that both the HER-2/neu and AR signaling pathways may contribute to development of metastatic disease. The subset of prostate tumors with increased HER-2/neu and AR levels may benefit from treatment strategies that target both signaling pathways.     

Intravascular hemolysis in patients with new-generation prosthetic heart valves: a prospective study

OBJECTIVE: A prospective clinical study was designed to assess the frequency and severity of intravascular hemolysis in patients with new-generation, normally functioning prosthetic heart valves. METHODS: Hemolysis was evaluated in 172 patients with a mechanical prosthesis (53 CarboMedics and 119 Sorin Bicarbon) and in 106 patients with a bioprosthesis (15 St Jude Medical Toronto, 19 Baxter Perimount, and 72 Medtronic Mosaic) in the aortic position, mitral position, or both. Aortic valve replacement was performed in 206 patients, mitral valve replacement in 59 patients, and double valve replacement in 13 patients. The presence of hemolysis was assessed on the basis of the level of serum lactic dehydrogenase and serum haptoglobin and the presence and amount of reticulocytes and schistocytes in the peripheral blood. Severity of intravascular hemolysis was estimated on the basis of serum lactic dehydrogenase. Clinical, echocardiographic, and hematologic evaluations were performed 1, 6, and 12 months after discharge. RESULTS: None of the 278 patients experienced decompensated anemia, whereas at 12 months, mild subclinical hemolysis was identified in 49 patients, 44 (26%) with a mechanical prosthesis and 5 (5%) with a bioprosthesis (P <.001). At multivariate analysis, independent predictors of the presence of subclinical hemolysis were mitral valve replacement (P <.001), use of a mechanical prosthesis (P =.002), and double valve replacement (P =.02). Frequency of hemolysis in patients with stented aortic bioprostheses was 3%, whereas it was absent in those with stentless valves. Among mechanical valve recipients, double versus single valve replacement (P =.04) and mitral versus aortic valve replacement (P =.05) were correlated with the presence of hemolysis; double valve recipients also showed a more severe degree of hemolysis (P =.03). In patients with a Sorin Bicarbon prosthesis, hemolysis was less frequent (22% vs 34%, P =.09) and severe (P <.001) than in those with a CarboMedics prosthesis. CONCLUSIONS: In normally functioning prosthetic heart valves, subclinical hemolysis is a frequent finding. A low incidence of hemolysis is found in stented biologic prostheses, and it is absent in stentless aortic valves. Modifications of valve design may contribute to minimize the occurrence of hemolysis in mechanical prostheses.     

The pre-Vesalian kidney: Gabriele Zerbi, 1445-1505

Gabriel Zerbi was born in Verona in 1445 and died in Dalmatia in 1505. He was professor of philosophy in Padua at the age of 22, and moved to Bologna where he became professor of medicine and philosophy. In Rome at the time of Sixtus V and Innocentius VIII, he was archiater and professor of medicine. He completed his academic career in Padua where he worked from 1494 to 1505 with a salary of 600 florins a month. A man of vast culture, a philosopher, physician and professor of medicine, he wrote many books: (1) Questiones Metaphysicae; (2) Gerentocomia; (3) De Cautelis Medicorum; (4) Liber anatomiae corporis humani et singulorum membrorum illius; (5) De anatomia infantiis et porci ex traditione Cophonis, and (6) Libellus de preservatione corporum a passione calculosa. His contribution to anatomy was superb. Through him the discipline became the basis of modern medicine. The core of this article deals with some passages of Zerbi's chapters on the anatomy of the kidneys and bladder.     

Asymmetric dimethyl-arginine (ADMA) response to inflammation in acute infections.

BACKGROUND AND METHODS: The endogenous inhibitor of nitric oxide synthase (NOs) asymmetrical dimethyl-arginine (ADMA) has been implicated as a possible modulator of inducible NOs during acute inflammation. We examined the evolution in the plasma concentration of ADMA measured at the clinical outset of acute inflammation and after its resolution in a series of 17 patients with acute bacterial infections. RESULTS: During the acute phase of inflammation/infection, patients displayed very high levels of C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin and nitrotyrosine. Simultaneous plasma ADMA concentration was similar to that in healthy subjects while symmetric dimethyl-arginine (SDMA) levels were substantially increased and directly related with creatinine. When infection resolved, ADMA rose from 0.62 +/- 0.23 to 0.80 +/- 0.18 micromol/l (+29%, P = 0.01) while SDMA remained unmodified. ADMA changes were independent on concomitant risk factor changes and inversely related with baseline systolic and diastolic pressure. Changes in the ADMA/SDMA ratio were compatible with the hypothesis that inflammatory cytokines activate ADMA degradation. CONCLUSIONS: Resolution of acute inflammation is characterized by an increase in the plasma concentration of ADMA. The results imply that ADMA suppression may actually serve to stimulate NO synthesis or that in this situation plasma ADMA levels may not reflect the inhibitory potential of this methylarginine at the cellular level.