Kidney stones and the ketogenic diet: risk factors and prevention

A cohort study was performed of children started on the ketogenic diet for intractable epilepsy from 2000 to 2005 (n = 195). Children who developed kidney stones were compared with those without in terms of demographics, urine laboratory markers, and intervention with urine alkalinization (potassium citrate). Thirteen children (6.7%) developed kidney stones. The use of oral potassium citrate significantly decreased the prevalence of stones (3.2% vs 10.0%, P = .049) and increased the mean time on the ketogenic diet before a stone was first noted (260 vs 149 patient-months, P = .29). The prevalence of kidney stones did not correlate with younger age or use of carbonic anhydrate inhibitors (eg, topiramate or zonisamide) but trended toward higher correlation with the presence of hypercalciuria (92% vs 71%, P = .08). No child stopped the diet due to stones; in fact, the total diet duration was longer (median 26 vs 12 months, P < .001). Kidney stones continue to occur in approximately 1 in 20 children on the ketogenic diet, and no statistically significant risk factors were identified in this cohort. As oral potassium citrate was preventative, prospective studies using this medication empirically are warranted.     

Effects of Hepatitis C-Induced Liver Fibrosis on Survival in Kidney Transplant Candidates

We sought to investigate survival among kidney transplant candidates with varying degrees of liver fibrosis. We studied 108 patients with hepatitis C+ who underwent pre-kidney transplant liver biopsy (1992–2004). Eighteen patients had advanced fibrosis (bridging fibrosis or cirrhosis), and 90 had lesser degrees of fibrosis. Advanced fibrosis patients were younger and had lower prevalence of diabetes. Survival was similar between those with and without advanced fibrosis among all 108 patients (P = 0.92) and among the 58 patients who underwent kidney transplantation (P = 0.83). Fibrosis stage was associated with a 1.1 (0.72, 1.7; P = 0.65) adjusted hazards ratio for mortality among all 108 patients and a 0.64 (0.24, 1.73; P = 0.38) adjusted hazards ratio among the 58 patients who underwent kidney transplantation. These data support the premise that non-liver disease comorbidities are more important outcome determinants in this population. Kidney transplantation alone may be considered in patients with hepatitis C with compensated cirrhosis or bridging fibrosis.     

Ultrastructure of mononuclear phagocytes developing in liquid bone marrow cultures. A study on peroxidatic activity

Monoblasts, promonocytes, and macrophages in in vitro cultures of murine bone marrow were studied ultrastructurally, with special attention to peroxidatic activity. Monoblasts show peroxidatic activity in the rough endoplasmic reticulum and nuclear envelope as well as in the granules. The presence of peroxidatic activity in the Golgi apparatus could not be determined. Promonocytes have peroxidase-positive rough endoplasmic reticulum, Golgi apparatus, nuclear envelope, and granules, as previously reported. During culture, cells are formed with peroxidatic activity similar to that of monocytes or exudate macrophages (positive granules; negative Golgi apparatus, RER, and nuclear envelope); we call these cells early macrophages. In addition, transitional macrophages with both positive granules and positive RER, nuclear envelope, negative Golgi apparatus (as in exudate- resident macrophages in vivo), and mature macrophages with peroxidatic activity only in the RER and nuclear envelope (as in resident macrophages in vivo) were found. A considerable number of cells without detectable peroxidatic activity were also encountered. Our finding that macrophages with the peroxidatic pattern of monocytes (early macrophages), exudate-resident macrophages (transitional macrophages), and resident macrophages (mature macrophages), develop in vitro from proliferating precursor cells deriving from the bone marrow, demonstrates once again that resident macrophages in tissues originate from precursor cells in the bone marrow. Therefore, this conclusion can no longer be challenged on the basis of a cytochemical difference between monocytes and exudate macrophages on the one hand and resident macrophages on the other.     

Anemia in pediatric dialysis patients in End-Stage Renal Disease Network 5

To identify demographic and clinical characteristics associated with failure to achieve hemoglobin levels 11 g/dl in prevalent pediatric end-stage renal disease (ESRD) patients, a cross-sectional analysis of patient clinical data collected by the Mid-Atlantic Renal Coalition in conjunction with the 2000 and 2001 ESRD Clinical Performance Measures Projects was performed. Ninety-nine patients (mean age 12.6 years, SD 5.4) contributed 119 observations to this analysis. Of patients on hemodialysis, 36.6% were anemic, and 39.5% of patients on peritoneal dialysis (PD) were anemic. Associations between age, race, gender, assigned cause of ESRD, Kt/V, transferrin saturation, time on dialysis, serum albumin, dialysis modality, and the achievement of target hemoglobin were examined. In multivariate logistic regression analyses examining age, dialysis modality, time on dialysis, and serum albumin, each 1-year increase in age was significantly associated with hemoglobin levels <11 g/dl [adjusted odds ratio (OR) 1.18, 95% confidence interval (CI) 1.06–1.32] and PD patients were more than twice as likely to have hemoglobin levels <11 g/dl (adjusted OR 2.62, 95% CI 0.98–7.04). Patients on dialysis for 6 months or more were less likely to be anemic than those on dialysis for less than 6 months (adjusted OR 0.39, 95% CI 0.16–0.99). In conclusion, increasing age, dialysis for less than 6 months, and treatment with PD were predictive of anemia in this population.     

Nosocomial respiratory syncytial virus infection in Canadian pediatric hospitals: a Pediatric Investigators Collaborative Network on Infections in Canada Study

OBJECTIVE: To determine nosocomial transmission of respiratory syncytial virus (RSV) in Canadian pediatric hospitals, outcomes associated with nosocomial disease, and infection control practices. DESIGN: A prospective cohort study in the 1992 to 1994 winter respiratory seasons. SETTING: Nine Canadian pediatric university-affiliated hospitals. PARTICIPANTS: Hospitalized children with symptoms of lower respiratory tract infection (at least one of cough, wheezing, dyspnea, tachypnea, and apnea) and RSV antigen identified in a nasopharyngeal aspirate. RESULTS: Of 1516 children, 91 (6%) had nosocomial RSV (NRSV), defined as symptoms of lower respiratory tract infection and RSV antigen beginning >72 hours after admission. The nosocomial ratio (NRSV/[com-munity-acquired RSV {CARSV})] + NRSV) varied by site from 2.8% to 13%. The median length of stay attributable to RSV for community-acquired illness was 5 days, but 10 days for nosocomial illness. Four children with NRSV (4. 4%) died within 2 weeks of infection, compared with 6 (0.42%) with CARSV (relative risk = 10.4, 95% confidence interval: 3.0, 36.4). All sites isolated RSV-positive patients in single rooms or cohorted them. In a multivariate model, no particular isolation policy was associated with decreased nosocomial ratio, but gowning to enter the room was associated with increased risk of RSV transmission (incidence rate ratio 2.81; confidence interval: 1.65, 4.77). CONCLUSIONS: RSV transmission risk in Canadian pediatric hospitals is generally low. Although use of barrier methods varies, all sites cohort or isolate RSV-positive patients in single rooms. Children with risk factors for severe disease who acquire infection nosocomially have prolonged stays and excess mortality.     

Participation of immunoglobulins and complement components in the intracellular killing of Staphylococcus aureus and Escherichia coli by human granulocytes.

Immunoglobulins and complement components are required for optimal ingestion and optimal killing of microorganisms by granulocytes. The degree of opsonization of microorganisms necessary for their ingestion was lower than that required for the killing of these bacteria during the ingestion phase. Killing during this phase was found to depend mainly on the presence of heat-labile opsonins, probably C3b, present on the microorganisms. Extracellular immunoglobulin G (IgG) and C3b were indispensable for optimal intracellular killing after ingestion was complete. This was established with an assay permitting assessment of the course of the number of viable intracellular bacteria independent of the ingestion of new live bacteria. Maximal intracellular killing by human granulocytes of ingested catalase-positive (Staphylococcus aureus and Escherichia coli) or catalase-negative (Streptococcus pyogenes and S. pneumoniae) microorganisms was found only when fresh serum was present extracellularly. Killing was suboptimal in the absence of serum. With heat-inactivated serum, the killing index lay between the indices obtained in the presence and absence of fresh serum. The stimulatory activity of heat-inactivated serum was most probably due to the interaction of IgG with the Fc receptor on the granulocyte membrane, since IgG subclasses IgG1 and IgG3 as well as pFc fragments of IgG stimulated the intracellular killing to the same degree as heat-inactivated serum did. In addition, (Fab1)2 fragments of IgG did not stimulate killing, and reduced killing was observed in the presence of heat-inactivated serum after reduction of the number of Fc receptors. The extra stimulation of the killing process in the presence of fresh serum compared with heat-inactivated serum was due to the interaction between membrane receptors and complement--most probably C3b generated by both the classical and the alternative pathways of complement activation. This conclusion is based on results obtained with sera in which one or both complement pathways were blocked, on the restoration of the killing-stimulatory activity of C3-deficient serum after addition of fresh C3, and on the reduced killing observed in the presence of fresh serum after reduction of the number of C3 receptors by the use of pronase or antigranulocyte serum.     

Predictive Value of Asphericity in Pretherapeutic [<Superscript>111</Superscript>In]DTPA-Octreotide SPECT/CT for Response to Peptide Receptor Radionuclide Therapy with [<Superscript>177</Superscript>Lu]DOTATATE

Purpose

The purpose of this study was to assess the value of the spatial heterogeneity of somatostatin receptor (SSR) volume, quantified as asphericity (ASP), and to predict response to peptide receptor radionuclide therapy (PRRT) in patients with metastatic gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN).

Procedures

From June 2011 to May 2013, patients suffering from GEP-NEN who underwent pretherapeutic [¹¹¹In-DTPA⁰]octreotide scintigraphy (Octreoscan®) prior to [¹⁷⁷Lu-DOTA⁰-Tyr³]octreotate ([¹⁷⁷Lu]DOTATATE)-PRRT were enrolled in this retrospective evaluation. SSR expression in 20 NEN patients was qualitatively and quantitatively assessed using the Krenning score, the metastasis to liver uptake ratio (M/L ratio), and ASP at baseline. Response to PRRT was evaluated based on lesions, which were classified as responding lesions (RL) and non-responding lesions (NRL) after 4- and 12-month follow-ups. The values of the Krenning score, M/L ratio, and ASP for response prediction were compared by using the Mann-Whitney U test, Kruskal-Wallis test, and receiver operating characteristic (ROC) curves.

Results

Seventy-seven metastases (liver, n = 40; lymph node, n = 24; bone, n = 11; pancreas, n = 2) showed SSR expression. A higher ASP level was significantly associated with poorer response at both time points. ROC analyses revealed the highest area under the curve (AUC) for discrimination between RL and NRL for ASP after 4 months (AUC 0.97; p = 0.019) and after 12 months (AUC 0.96; p < 0.001), followed by the Krenning score (AUC 0.74; p = 0.082 and AUC 0.85; p < 0.001, respectively) and M/L ratio (AUC 0.77; p = 0.107 and AUC 0.82; p < 0.001). The optimal cutoff value for ASP was 5.12 % (sensitivity, 90 %; specificity, 93 %).

Conclusion

Asphericity of SSR-expressing lesions in pretherapeutic single-photon emission computed tomography with integrated computed tomography (SPECT/CT) is a promising parameter for predicting response to PRRT in gastroenteropancreatic neuroendocrine neoplasms.

     

Kidney and liver transplantation in children with fibrocystic liver–kidney disease: Data from the US Scientific Registry of Transplant Recipients: 1990–2010

The natural history and survival of children with fibrocystic liver–kidney disease undergoing solid organ transplantation have infrequently been described. We report outcomes in a cohort of US children with fibrocystic liver–kidney disease receiving solid organ transplants over 20 yr. Retrospective cohort study of pediatric transplant recipients with diagnoses of fibrocystic liver–kidney disease from 1/1990 to 3/2010, using data from the SRTR. Subjects were categorized by the first transplanted organ: LT, KT, or SLK. Primary outcomes were death, re‐transplant, transplant of the alternate organ, or initiation of dialysis. Seven hundred and sixteen subjects were transplanted in this period. Median age at first transplant was 9.7 yr. Of the LT, 14 (19%) required a second liver transplant at median of 0.2 yr, and five (7%) required kidney transplant or dialysis at a median of 9.0 yr. Of the KT, 188 (31%) required a second kidney transplant or dialysis at a median of 5.9 yr. Twenty‐nine (5%) subsequently received liver transplant at a median of 6.0 yr. Among patients in this registry, far more children underwent kidney than liver transplants. The risk of subsequently needing transplantation of an alternate organ was low.