Communications Biophysics

Contains research objectives and reports on six research projects split into three sections.National Institutes of Health (Grant 5 P01 NS13126-07)National Institutes of Health (Training Grant 5 T32 NS07047-05)National Institutes of Health (Training Grant 2 T32 NS07047-06)National Science Foundation (Grant BNS 77-16861)National Institutes of Health (Grant 5 R01 NS1284606)National Institutes of Health (Grant 5 T32 NS07099)National Science Foundation (Grant BNS77-21751)National Institutes of Health (Grant 5 R01 NS14092-04)Gallaudet College SubcontractKarmazin Foundation through the Council for the Arts at M.I.T.National Institutes of Health (Grant 1 R01 NS1691701A1)National Institutes of Health (Grant 5 R01 NS11080-06)National Institutes of Health (Grant GM-21189

Communications Biophysics

Contains reports on seven research projects split into three sections.National Institutes of Health (Grant 5 PO1 NS13126)National Institutes of Health (Grant 1 RO1 NS18682)National Institutes of Health (Training Grant 5 T32 NS07047)National Science Foundation (Grant BNS77-16861)National Institutes of Health (Grant 1 F33 NS07202-01)National Institutes of Health (Grant 5 RO1 NS10916)National Institutes of Health (Grant 5 RO1 NS12846)National Institutes of Health (Grant 1 RO1 NS16917)National Institutes of Health (Grant 1 RO1 NS14092-05)National Science Foundation (Grant BNS 77 21751)National Institutes of Health (Grant 5 R01 NS11080)National Institutes of Health (Grant GM-21189

Cryptococcus neoformans in organ transplant recipients: Impact of calcineurin-inhibitor agents on mortality

Variables influencing the risk of dissemination and outcome of Cryptococcus neoformans infection were assessed in 111 organ transplant recipients with cryptococcosis in a prospective, multicenter, international study. Sixty-one percent (68/111) of the patients had disseminated infection. The risk of disseminated cryptococcosis was significantly higher for liver transplant recipients (adjusted hazard ratio [HR], 6.65; P= .048). The overall mortality rate at 90 days was 14% (16/111). The mortality rate was higher in patients with abnormal mental status (P = .023), renal failure at baseline (P = .028), fungemia (P = .006), and disseminated infection (P = .035) and was lower in those receiving a calcineurin-inhibitor agent (P = .003). In a multivariable analysis, the receipt of a calcineurin-inhibitor agent was independently associated with a lower mortality (adjusted HR, 0.21; P = .008), and renal failure at baseline with a higher mortality rate (adjusted HR, 3.14; P = .037). Thus, outcome in transplant recipients with cryptococcosis appears to be influenced by the type of immunosuppressive agent employed. Additionally, discerning the basis for transplant type–specific differences in disease severity has implications relevant for yielding further insights into the pathogenesis of C. neoformans infection in transplant recipients

Identifying Predictors of Central Nervous System Disease in Solid Organ Transplant Recipients With Cryptococcosis

BACKGROUND: CSF analysis is often deferred in patients with cryptococcal disease, particularly in the absence of neurologic manifestations. We sought to determine if a subset of SOT recipients with high likelihood of CNS disease could be identified in whom CSF analysis must be performed. METHODS: Patients comprised a multicenter cohort of SOT recipients with cryptococcosis. RESULTS: Of 129 of 146 (88%) SOT recipients with cryptococcosis who underwent CSF analysis, 80 (62%) had CNS disease. In the overall study population, abnormal mental status, time to onset of cryptococcosis >24 months post-transplantation (late-onset disease), serum cryptococcal antigen titer >1:64, and fungemia were independently associated with an increased risk of CNS disease. Of patients with abnormal mental status, 95% had CNS cryptococcosis. When only patients with normal mental status were considered, three predictors (serum antigen titer >1:64, fungemia, and late-onset disease) independently identified patients with CNS cryptococcosis; the risk of CNS disease was 14% if none, 39% if one, and 94% if two of the aforementioned predictors existed (χ(2) for trend p<0.001). CONCLUSIONS: CSF analysis should be strongly considered in SOT recipients with cryptococcosis who have late-onset disease, fungemia, or serum cryptococcal antigen titer >1:64 even in the presence of normal mental status

Calcineurin Inhibitor Agents Interact Synergistically with Antifungal Agents In Vitro against Cryptococcus neoformans Isolates: Correlation with Outcome in Solid Organ Transplant Recipients with Cryptococcosis▿

Synergistic interactions were observed between CIs and antifungal agents against 53 (90%) of 59 Cryptococcus neoformans isolates from solid organ transplant recipients with cryptococcosis and may account for better outcomes in patients with cryptococcosis receiving these immunosuppressive agents

Cutaneous cryptococcosis in solid organ transplant recipients

Clinical manifestations, treatment, and outcomes of cutaneous cryptococcosis in solid organ transplant (SOT) recipients are not fully defined. In a prospective cohort comprising 146 SOT recipients with cryptococcosis, we describe the presentation, antifungal therapy, and outcome of cutaneous cryptococcal disease. Cutaneous cryptococcosis was documented in 26/146 (17.8%) of the patients and manifested as nodular/ mass (34.8%), maculopapule (30.4%), ulcer/pustule/abscess (30.4%), and cellulitis (30.4%) with 65.2% of the skin lesions occurred in the lower extremities. Localized disease developed in 30.8% (8/26), and disseminated disease in 69.2% (18/26) with involvement of the central nervous system ( 88.9%, 16/18), lung (33.3%, 6/18 ), or fungemia (55.6%, 10/18). Fluconazole (37.5%) was employed most often for localized and lipid formulations of amphotericin B (61.1%) for disseminated disease. Overall mortality at 90 days was 15.4% (4/26) with 16.7% in disseminated and 12.5% in localized disease (P = 0.78). SOT recipients who died were more likely to have renal failure ( 75.0% vs. 13.6%, P = 0.028), longer time to onset of disease after transplantation (87.5 vs. 22.6 months, P = 0.023), and abnormal mental status (75% vs. 13.6%, P = 0.028) than those who survived. Cutaneous cryptococcosis represents disseminated disease in most SOT recipients and preferentially involves the extremities. Outcomes with appropriate management were comparable between SOT recipients with localized and disseminated cryptococcosis