Person:

Vagefi, Parsia A.

Background:. BK virus (BKV) infection is a common complication following kidney transplantation. Immunosuppression reduction is the cornerstone of treatment while adjuvant drugs have been tried in small uncontrolled studies. We sought to examine our center's experience with the use of ciprofloxacin in patients with persistent BKV infection. Methods:. Retrospective evaluation of the effect of a 30-day ciprofloxacin course (250 mg twice daily) on BKV infection in kidney transplant recipients who had been diagnosed with BK viruria ≥106 copies/mL and viremia ≥500 copies/mL and in whom the infection did not resolve after immunosuppression reduction and/or treatment with other adjuvant agents. BKV in plasma and urine was evaluated after 3 months following treatment with ciprofloxacin. Results. Nine kidney transplant recipients received ciprofloxacin at a median of 130 days following the initial reduction in immunosuppression. Three patients showed complete viral clearance and another 3 had a ≥50% decrease in plasma viral load. No serious adverse events secondary to ciprofloxacin were reported and no grafts were lost due to BKV up to 1 year after treatment. Conclusion. Ciprofloxacin may be a useful therapy for persistent BKV infection despite conventional treatment. Randomized trials are required to evaluate the potential benefit of this adjuvant therapy.

Background. Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disorder leading to end-stage renal failure. The objective of this study was to evaluate a longitudinal experience of kidney transplantation for ADPKD. Methods. A single center retrospective review of patients undergoing kidney transplantation was conducted, with comparisons across two time periods: early (02/2000–04/2007, n = 66) and late (04/2007–08/2012, n = 67). Results. Over the 13.5-year study period, 133 patients underwent transplantation for ADPKD. Overall, no significant difference between the early and late group with regard to intraoperative complications, need for reoperation, readmissions within 30 days, delayed graft function, and mortality was noted. There was a trend towards increase in one-year graft survival (early 93.1% versus late 100%, P = 0.05). In the early group, 67% of recipients had undergone aneurysm screening, compared to 91% of recipients in the late group (P < 0.001). Conclusions. This study demonstrates consistent clinical care with a trend towards improved rates of one-year graft survival. Interestingly, we also note a significantly higher use of cerebral imaging over time, with the majority that were detected requiring surgical intervention which may justify the current practice of nonselective radiological screening until improved screening criteria are developed.

Despite the success of antiretroviral therapy (ART), it does not cure Human Immunodeficiency Virus (HIV) and discontinuation results in viral rebound. Follicular dendritic cells (FDC) are in direct contact with CD4+ T cells and they retain intact antigen for prolonged periods. We found that human FDC isolated from patients on ART retain infectious HIV within a non-degradative cycling compartment and transmit infectious virus to uninfected CD4 T cells in vitro. Importantly, treatment of the HIV+ FDC with a soluble complement receptor 2 purges the FDC of HIV virions and prevents viral transmission in vitro. Our results provide an explanation for how FDC can retain infectious HIV for extended periods and suggest a therapeutic strategy to achieve cure in HIV-infected humans.

Objective: To assess changing patterns in the detection and outcomes of pancreatic neuroendocrine neoplasms (PNENs). Design: Retrospective review from May 21, 1977, through September 16, 2005. Setting: Massachusetts General Hospital, a tertiary care center. Patients: We evaluated 168 patients (51% male; mean age, 56 years) who underwent surgery for histologically confirmed PNENs. Main Outcome Measures: Surgical outcomes, survival, and changes in presentation of PNENs in 2 time groups: 1977-1999 (77 patients) and 2000-2005 (91 patients). Results: Ninety-eight patients (58.3%) had nonfunctioning PNENs, 86 of which were incidental. Insulinomas were the most common type of functional neoplasm (33.3%), followed by gastrinomas and glucagonomas; 12 patients (7.1%) had multiple endocrine neoplasia type 1. Of the neoplasms, 107 (63.7%) were located in the pancreatic body or tail. A pancreaticoduodenectomy was performed in 37 patients (22.0%), distal pancreatectomy was done in 88 (52.4%), and the rest had either middle segment pancreatectomy or enucleation. There were no operative deaths. We classified 76.8% of neoplasms as benign; of those classified as malignant, 25.6% had liver metastases. Of the patients, 10.1% received adjuvant therapy. Complete follow up was available in 90.5% of patients (mean, 63.3 months). Five- and 10-year actuarial survival rates were 77% and 62%, respectively. Incidentally discovered nonfunctioning neoplasms were significantly more frequent in the last 5 years (60.4% vs 40.3%; = .007), with a trend toward smaller neoplasms (mean, 4.2 cm vs 5.6 cm; = .19) and lesser likelihood of malignancy (21.8% vs 40.0%; = .08). Conclusions: We report a large single-center experience with PNENs. Increasing numbers of PNENs are being resected, largely owing to the incidental detection of nonfunctioning neoplasms. This may lead to the treatment of smaller and less malignant neoplasms. Pancreatic neuroendocrine neoplasms (PNENs) are rare entities with a wide spectrum of clinical presentation. The secretion of hormonal products into the blood results in functional neoplasms that cause clinical symptoms, and thus they are classified according to their hormonal product. In contrast, nonfunctional neoplasms do not secrete a hormonal product with a known clinical effect, and usually disease does not become apparent until they are large enough to cause impingement of adjacent structures with symptoms of jaundice, abdominal pain, or weight loss. Pancreatic neuroendocrine neoplasms differ both biologically and clinically from pancreatic adenocarcinoma. In comparison to pancreatic adenocarcinoma, in which the 5-year and 10-year actual survival rates in patients who have undergone resection remain very low (15% and 4%, respectively), most PNENs are reported to display an indolent course and are associated with longer survival. The natural history of PNENs is largely unknown. Although they are found in 0.5% to 1.5% of autopsies, they occur with an annual incidence of only about 5 to 10 cases per million persons, which is thought to reflect the asymptomatic nature of most of these neoplasms. Currently, complete surgical resection is thought to be the only curative treatment for PNENs. Our study aims to describe a large single-center experience with the operative management of PNENs, including analysis of clinical presentation, operative course, surgical morbidity, and long-term survival.