Hepatitis C and autoimmunity: a therapeutic challenge

Hepatitis C virus (HCV) infection causes not only acute and chronic liver disease, but also extrahepatic symptoms. To our knowledge, this is the first case report of a patient who developed simultaneously subacute cutaneous lupus erythematosus and a small CD20+ B-cell clone because of chronic HCV infection and relapse after standard of care therapy (pegylated interferon plus ribavirin). Treatment with rituximab, a chimeric anti-CD20 monoclonal antibody, was successful.     

Management of Anemia in Children Receiving Chronic Peritoneal Dialysis

Little information exists regarding the efficacy, modifiers, and outcomes of anemia management in children with CKD or ESRD. We assessed practices, effectors, and outcomes of anemia management in 1394 pediatric patients undergoing peritoneal dialysis (PD) who were prospectively followed in 30 countries. We noted that 25% of patients had hemoglobin levels below target (<10 g/dl or <9.5 g/dl in children older or younger than 2 years, respectively), with significant regional variation; levels were highest in North America and Europe and lowest in Asia and Turkey. Low hemoglobin levels were associated with low urine output, low serum albumin, high parathyroid hormone, high ferritin, and the use of bioincompatible PD fluid. Erythropoiesis-stimulating agents (ESAs) were prescribed to 92% of patients, and neither the type of ESA nor the dosing interval appeared to affect efficacy. The weekly ESA dose inversely correlated with age when scaled to weight but did not correlate with age when normalized to body surface area. ESA sensitivity was positively associated with residual diuresis and serum albumin and inversely associated with serum parathyroid hormone and ferritin. The prevalence of hypertension and left ventricular hypertrophy increased with the degree of anemia. Patient survival was positively associated with achieved hemoglobin and serum albumin and was inversely associated with ESA dose. In conclusion, control of anemia in children receiving long-term PD varies by region. ESA requirements are independent of age when dose is scaled to body surface area, and ESA resistance is associated with inflammation, fluid retention, and hyperparathyroidism. Anemia and high ESA dose requirements independently predict mortality.Almost three decades after the advent of recombinant erythropoietin, the management of renal anemia has become a recent focus of attention and changing paradigms. Whereas correction of hemoglobin (Hb) levels to near-normal has previously been recommended on the basis of association studies linking more severe anemia to morbidity and mortality with dialysis,^1–3 interventional clinical trials consistently demonstrate that near-normalization of Hb increases the risk of vascular events and mortality in adults receiving maintenance hemodialysis and in those with CKD who are not undergoing dialysis.^4–6 This has prompted ongoing reevaluation and revisions of treatment targets in patients exposed to erythropoiesis-stimulating agents (ESAs).⁷The appropriateness of applying treatment recommendations established in adult hemodialysis populations at high cardiovascular risk and adults with CKD to children undergoing dialysis is questionable because cardiovascular events are far less common in children with CKD. Furthermore, two thirds of children requiring dialysis initially opt for peritoneal dialysis (PD), and there are no systematic studies in the adult PD population to inform the optimal Hb target range in these patients. The risk profile of patients receiving PD may differ from that of the hemodialysis setting because of the absence of dialysis-induced intermittent hemoconcentration and lack of contact activation of the complement and coagulation systems.Further aspects to consider in pediatric anemia management are the greater physical activity of children and the need for optimal cognitive functioning at school.^8,9 The significant physiologic variation of the normal Hb range with age¹⁰ and the relative ESA sensitivity that reportedly increases with age during early childhood are also noteworthy.¹¹The registry of the International Pediatric Peritoneal Dialysis Network (IPPN) prospectively collects detailed clinical, biochemical, dialysis, and medication-related information (including ESA types and doses and modalities of iron supplementation) from a substantial number of children undergoing long-term PD around the world. In-depth analysis of this unique database has allowed us to (1) gain insight into the demographic characteristics of renal anemia and its treatment in the pediatric PD population worldwide, (2) explore the relationship between ESA dose requirements and body dimensions, (3) identify factors contributing to ESA resistance in children, and (4) associate anemia control with patient outcomes.     

Blood pressure tracking in children and adolescents

Background

High blood pressure is a major risk factor for cardiovascular disease. Blood pressure tracking could help to identify individuals with potential hypertension. Therefore, we have asked whether or not tracking was of predictive value for the development of hypertension in early life.

Methods

Blood pressure was routinely measured in 13,261 children and adolescents in outpatient clinics as well as during hospitalization. In one analysis, 568 individuals with elevated and normotensive blood pressure values were evaluated after 2, 4, and 6 years of follow-up. In a second analysis, 2,157 individuals with normotensive blood pressure were examined in a paired t test.

Results

The follow-up analysis showed a significant tracking effect. However, the Pearson correlation coefficients of the systolic and diastolic blood pressure standard deviation scores (SDS) decreased over time. Upon the follow-up after 6 years, 35.6 % of the children and adolescents with elevated blood pressure values remained in the elevated range group. Of the children within the normotensive blood pressure range, 80.4 % remained normotensive after 6 years. Children with normotensive blood pressure showed a stronger tracking than those who had had one hypertensive blood pressure reading. Children with higher body mass index (BMI) at follow-up changed blood pressure SDS track from initially normal to higher blood pressure values.

Conclusions

Blood pressure tracking in children and adolescents is moderate. We conclude that the predictive power of a single hypertensive blood pressure measurement during a single visit is rather small, and thus repetitive measurements across several consecutive visits are necessary.     

Laparoscopic Colorectal Surgery for Obese Patients: Decreased Conversions with the Hand-Assisted Technique

Background

Laparoscopic surgery benefits obese patients but technical difficulties associated with suboptimal exposure and access in these subjects may prompt conversion to open surgery. Hand-assisted laparoscopic surgery (HALS) confers advantages over standard laparoscopy (LAP) by facilitating tactile feedback, assisted dissection, and retraction. These benefits could be particularly valuable in obese patients, allowing completion of difficult laparoscopic procedures in this subgroup. Our aim was to compare intra-operative and post-operative outcomes of HALS and LAP approaches in obese patients undergoing colorectal resection at our institution.

Methods

A retrospective study of a prospectively maintained laparoscopic colorectal surgery database was performed. HALS and LAP cases performed in obese patients (body mass index (BMI)?>30) were identified and compared for the following outcomes: operative time, intra-operative complications, rate of conversion to open, blood loss, length of stay, post-operative morbidity, and mortality. Outcomes for the converted patients were included on an intention-to-treat basis for all primary analyses. A secondary analysis of nonconverted and converted cases was also performed.

Results

Over a 5-year period, 496 obese patients underwent laparoscopic colorectal resection; 86 HALS and 410 LAP cases. The two groups were comparable in terms of age, gender, BMI, and indications for surgery. Conversion to open surgery was less often necessary in HALS compared to LAP cases (3.5 % vs. 12.7 %, p?=?0.014). The LAP group had a significantly smaller incision length for specimen extraction (HALS (7.0?±?1.3 cm) vs. LAP (5.7?±?2.1 cm), p?<?0.001). Length of stay, operative time, morbidity, and mortality rates were comparable between the two groups.

Conclusion

In obese patients who require colectomy, the HALS approach increases the likelihood of a successful minimally invasive operation. At the cost of a clinically negligible increase in incision length, HALS may save a high-risk group conversion to formal laparotomy and the adverse outcomes related to this.     

Experimental intracerebral hemorrhage: Description of a double injection model in rats

Abstract

For experimental purposes, f/ie mosf common technique of producing an intracerebral hematoma in rats is the injection of unclotted autologous blood. All modifications of this model share the problem that size and extension of the hematoma are not reproducible, because the injected blood either ruptures into the ventricular system or it extends to the subarachnoid or subdural space. Therefore a double injection model of experimental intracerebral hemorrhage in rats has been developed using 19 male Sprague-Dawley rats. After inducing anesthesia a cannula was stereotactically placed into the caudate nucleus and an intracerebral hematoma was produced with the double injection method in which first a small amount of fresh autologous blood is injected which is allowed to clot (preclotting) in order to block the way back along the needle track; the actual hematoma is produced in a second step of the injection. The clot volume was measured on stained serial sections. A total injection volume of 50 \i! of autologous blood produced intracerebral hematomas of 41.1 ± 10.0 \i\ and of similar shapes. The double injection method allows to generate reproducible hematomas in rats. This new model of intracerebral hemorrhage will allow further investigation of fibrinolytic and cytoprotective therapies. [Neurol Res 1996; 18: 475-477]