Travel Distance and Home Dialysis Rates in the United States

♦ Introduction: Rural residence is associated with increased peritoneal dialysis (PD) utilization. The influence of travel distance on rates of home dialysis utilization has not been examined in the United States. The purpose of this study was to determine whether travel distances to the closest home and in-center hemodialysis (IHD) facilities are a barrier to home dialysis.♦ Methods: This was a retrospective cohort study of patients aged ≥ 18 years initiating dialysis between 2005 and 2011. Unadjusted PD and home hemodialysis (HHD) rates were compared by travel distances to both the closest home dialysis and closest IHD facilities. Adjusted PD and HHD utilization rates were examined using multivariable logistic regression models.♦ Results: There were 98,608 patients in the adjusted analyses. 55.5% of the dialysis facilities offered home dialysis. IHD, PD and HHD patients traveled median distances of 5.4, 3.5 and 6.6 miles respectively to their initial dialysis facilities. Unadjusted analyses showed an increase in PD rates and decrease in HHD rates with increased travel distances. Adjusted odds of PD and HHD were 1.6 and 1.2 respectively for a ten mile increase in distance to the closest home dialysis facility, while for distances to the closest IHD facility the odds ratios for both PD and HHD were 0.7 (all p < 0.01).♦ Conclusions: In metropolitan areas, PD and HHD generally increased with increased travel distance to the closest home dialysis facility and decreased with greater distance to an IHD facility. Examination of travel distances to PD and HHD facilities separately may provide further insight on specific barriers to these modalities which can serve as targets for future studies examining expansion of home dialysis utilization.     

Perinatal mortality in twin pregnancies

Many patients with fibromyalgia syndrome suffer for years before the proper diagnosis is made. Because their symptoms mimic those of more serious diseases, a careful search for other causes is essential. Dr Romano presents a method of systematic evaluation to aid diagnosis and also suggests a number of approaches to an effective treatment plan.     

Addition of Plasmapheresis Decreases the Incidence of Acute Antibody-Mediated Rejection in Sensitized Patients with Strong Donor-Specific Antibodies

Background and objectives: The objective of this study was to investigate the effects of desensitization protocols using intravenous Ig with or without plasmapheresis in patients with donor-specific anti-HLA antibodies on prevention of antibody-mediated rejection and downregulation of donor-specific antibodies.Design, setting, participants, & measurements: Thirty-five complement-dependent cytotoxicity T cell cross-match–negative but complement-dependent cytotoxicity B cell and/or flow cytometry cross-match–positive kidney transplant recipients were treated with high-dosage intravenous Ig plus Thymoglobulin induction treatment. Donor-specific antibody strength was stratified as strong, medium, or weak by Luminex flow beads. Group 1 patients had weak/moderate and group 2 strong donor-specific antibodiesResults: Whereas no group 1 patients had acute rejection, 66% of group 2 had acute rejection (44% antibody-mediated rejection, 22% cellular rejection). The protocol was then changed to the addition of peritransplantation plasmapheresis to patients with strong donor-specific antibodies (group 3). This change resulted in a dramatic decrease in the acute rejection rate to 7%. During a median 18 mo of follow-up, patient survival was 100, 100, and 93% and graft survival was 100, 78, and 86% in groups 1, 2, and 3, respectively. During follow-up, 17 (52%) patients lost donor-specific antibodies completely, and 10 (30%) lost some of donor-specific antibodies and/or decreased the strength of existing donor-specific antibodies.Conclusions: These results indicated that in patients with strong donor-specific antibodies, the addition of plasmapheresis to high-dosage intravenous Ig decreases the incidence of acute rejection. The majority of the patients, whether they received intravenous Ig alone or with plasmapheresis, lost their donor-specific antibodies during follow-up.Donor-specific anti-HLA antibodies (DSA) in patients who are sensitized through pregnancy, previous blood transfusions, or organ transplantation is an important obstacle in kidney transplantation. Sensitized patients wait longer on the deceased-donor transplantation list, may not receive a transplant, and may have greater morbidity and mortality. Some sensitized patients may have living donor candidates, but transplantation cannot be performed because of cross-match positivity. Recent desensitization protocols using the combination of plasmapheresis (PP) or immunoadsorption to remove DSA and/or intravenous Ig (IVIG) and rituximab to downregulate antibody-mediated immune responses have made kidney transplantation feasible by abrogating complement-dependent cytotoxicity (CDC) T cell cross-match positivity. In previous studies, two protocols were examined: High-dosage IVIG (2.0 g/kg) (1–3) and PP with low-dosage IVIG (100 mg/kg after each PP session) (4–8); however, acute antibody-mediated rejection (AMR) continued to be an important barrier and was still observed in at least 30 to 40% of the recipients included in these desensitization protocols, even when rituximab was added to the protocol.Whereas CDC T cell cross-match positivity is an absolute contraindication to kidney transplantation, the clinical significance of CDC B cell or flow cytometry (FC) T and/or B cell cross-match positivity are less clear. Most studies have demonstrated that CDC T cell cross-match–negative but CDC B or FC T/B cell cross-match–positive patients with DSA are at higher risk for developing acute cellular, antibody-mediated, and chronic rejection and graft loss (9,10). The role of desensitization protocols for these patients has not been studied in a large cohort. We previously reported our initial experience using low-dosage IVIG (300 mg/kg) and Thymoglobulin induction treatment in 15 patients (11,12). Because of early AMR in three patients, the IVIG dosage was increased to a total of 2.0 mg/kg in subsequent patients. Now, we present our experience in CDC T cell–negative but CDC B cell or FC T and/or B cell cross-match–positive kidney transplant recipients with DSA, who were stratified according to mean fluorescence indices of Luminex flow beads. The results showed that patients with strong DSA were at much higher risk for developing acute AMR early after transplantation, and the addition of peritransplantation PP to high-dosage IVIG and Thymoglobulin treatment significantly decreased the incidence of AMR. The majority of the patients, whether they received IVIG alone or with PP, lost DSA during follow-up.     

Neurotensin is an autocrine trophic factor stimulated by androgen withdrawal in human prostate cancer.

After therapeutic hormone deprivation, prostate cancer cells often develop androgen-insensitive growth through mechanisms thus far undefined. Neuropeptides have been previously implicated as growth factors in some prostate cancers. Here, we demonstrate that androgen-sensitive LNCaP human prostate cancer cells produce and secrete neurotensin following androgen withdrawal. We show that while LNCaP cells express the neurotensin receptor, only androgen-deprived cells exhibit a growth response to exogenous neurotensin. We further demonstrate that androgen-stimulated cells may be refractory to exogenous neurotensin due to androgen induction of a metalloprotease active toward neurotensin. Thus, prostate cancer cells deprived of androgen develop an alternative autocrine growth mechanism involving neurotensin.     

Prevalence of intestinal parasitic pathogens in HIV-seropositive individuals in Northern India

To assess the prevalence of intestinal parasitic infections in human immunodeficiency virus (HIV)-seropositive subjects, fecal samples were collected from 120 HIV-seropositive patients and were analyzed for various intestinal parasites. Thirty-six patients (30%) were found to harbor an intestinal parasite. Cryptosporidium parvum was the most common (10.8%), followed by Giardia lamblia (8.3%). Cyclospora cayetanensis and Blastocystis hominis each were detected in 3.3% of the patients, while Isospora belli and Enterocytozoon bieneusi were each detected in 2.5% of the patients. The other parasites observed were Entamoeba histolytica/E. dispar in two cases and hookworm ova in one patient. Of the 36 patients who tested positive for intestinal parasites, 27 (75%) had diarrhea. The most common parasite, which was associated with diarrhea, was C. parvum. The present study highlights the importance of testing for intestinal parasites in patients who are HIV-positive, and emphasizes the necessity of increasing awareness among clinicians regarding the occurrence of these parasites in this population.     

Inhibition of hepatitis B virus DNA replicative intermediate forms by recombinant interferon-γ

AIM: To evaluate the in vitro anti-HBV activity of recombinant human IFN-γ, alone and in combination with lamivudine.METHODS: A recombinant baculovirus-HBV/HepG2 culture system was developed which could support productive HBV infection in vitro. Expression of HBsAg and HBeAg in infected HepG2 culture medium was detected by commercial enzyme immunoassays. HBV DNA replication intermediates were detected in infected cells by Southern hybridization and viral DNA load was determined by dot hybridization.RESULTS: IFN-γ at 0.1 to 5 μg/L efficiently down regulated HBsAg expression in transduced HepG2 cells.At 5 μg/L, IFN-γ also suppressed HBV DNA replication in these cells. While treatment with a combination of lamivudine and IFN-γ showed no additive effect,sequential treatment first with lamivudine and then IFN-γ was found to be promising. In this culture system the best HBV suppression was observed with a pulse of 2 μmol/L lamivudine for two days, followed by 1 μg/L IFN-γ for another four days. Compared to treatment with lamivudine alone, the sequential use of 0.2 μmol/L lamivudine for two days, followed by 5 μg/L IFN-γ for six days showed a 72% reduction in HBV cccDNA pool.CONCLUSION: This in vitro study warrants further evaluation of a combination of IFN-γ and lamivudine,especially in IFN-α non-responder chronic hepatitis B patients. A reduced duration of lamivudine treatment would also restrict the emergence of drug-resistant HBV mutants.