BACKGROUND.: Polyomavirus-associated nephropathy (PVAN) is an important cause of kidney graft loss but there is no consensus on its management. This study aimed to systematically document all published treatments for PVAN to determine the most effective therapy. METHODS.: A computerized search in MEDLINE, EMBASE, and Cochrane databases (1950-2008) was performed. References from review articles and published abstracts from the American Transplant Congress (2005-2008) were also included. Study selection criteria included (a) population: adult (>18 years) kidney-only, primary or repeat renal transplant recipients; (b) setting: polyoma viruria, viremia or biopsy-proven PVAN or both; and (c) treatment: immunosuppression reduction alone or with adjuvant agents. The primary outcome was graft failure rate, and secondary outcomes included acute rejection rate, elimination of viruria and viremia, graft function, patient survival, and adverse events. RESULTS.: Of 555 identified citations, 40 studies examining the effect of immunosuppression reduction alone or in combination with cidofovir, leflunomide, intravenous immunoglobulin, or ciprofloxacin were included for appraisal. Pooled results found a death-censored graft loss rate of 8/100 patient-years for immunosuppression reduction alone and 8 and 13/100 patient-years for the addition of cidofovir or leflunomide, respectively. CONCLUSIONS.: There does not seem to be a graft survival benefit of adding cidofovir or leflunomide to immunosuppression reduction for the management of PVAN. However, the evidence base is poor and highlights the urgent need for adequately powered randomized trials to define the optimal treatment of this important condition.

National Institutes of Health. (PROSPERO: CRD42016052716).

Objective Since publication of the ARMA trial in 2000, use of tidal volumes (VT) ≤6 mL/kg predicted body weight (PBW) with corresponding plateau airway pressures (PPlat) ≤30 cmH2O has been advocated for acute lung injury (ALI). However, compliance with these recommendations is unknown. We therefore investigated VT (mL/kg PBW) and PPlat (cmH2O) practices reported in studies of ALI since ARMA using a systematic literature review (i.e. not a meta-analysis). Data Sources PubMed, Scopus, and EMBASE. Study Selection Randomized controlled trials (RCTs) and non-randomized studies (NRS) enrolling ALI patients from May 2000 to June 2013 and reporting VT. Data Extraction Whether the study was an RCT or NRS and performed or not at an ARDSNetwork center; in RCTs, the pre- and post-randomization VT (mL/kg PBW) and PPlat (cmH2O) and whether a VT protocol was used post-randomization; in NRSs, baseline VT and PPlat. Data Synthesis Twenty-two RCTs and 71 NRSs were included. Since 2000 at ARDSNetwork centers, routine VT was similar comparing RCTs and NRSs (p=0.25) and unchanged over time (p=0.75) with a mean value of 6.81(95%CI: 6.45,7.18). At non-ARDSNetwork centers routine VT was also similar when comparing RCTs and NRSs (p=0.71), but decreased (p=0.001); the most recent estimate for it was 6.77(6.22,7.32). All VT estimates were significantly >6 (p≤0.02). In RCTs employing VT protocols, routine VT was reduced in both ARDSNetwork (n=4) and non-ARDSNetwork (n=11) trials (p≤0.01 for both), but even post-randomization was >6 [6.47(6.29,6.65) and 6.80(6.42,7.17), respectively; p≤0.0001 for both)]. In 59 studies providing data, routine PPlat, averaged across ARDSNetwork or non-ARDSNetwork centers was significantly <30 (p≤0.02). Conclusion For clinicians treating ALI since 2000, achieving VT ≤6 mL/kg PBW may not have been as attainable or important as PPlat ≤30 cmH2O.. If so, there may be equipoise to test if VT ≤6 mL/kg PBW are necessary to improve ALI outcome.

BackgroundAlthough anthrax immune globulin (AIG) improved survival in antibiotic-treated Bacillus anthracis-challenged animal models, whether it adds to the benefit of conventional hemodynamic support for B. anthracis toxin-associated shock is unknown.MethodsWe therefore tested AIG in sedated, mechanically ventilated canines challenged with 24-h B. anthracis lethal and edema toxin infusions and supported for 96 h with a previously demonstrated protective regimen of titrated normal saline and norepinephrine.ResultsCompared to controls, proportional survival (%) was increased with AIG treatment started 4 h before (33 vs. 100%, n = 6 each) or 2 h (17 vs. 86%, n = 6 and 7 respectively) or 5 h (0 vs. 67%, n = 3 each) after the start of toxin (p ≤ 0.05) and overall [3 survivors of 15 controls (20%) vs. 14 of 16 AIG animals (88%); p = 0.006]. Averaged across treatment times, AIG increased blood pressure at 48 h and decreased norepinephrine requirements at 72 h (p ≤ 0.02), increased left ventricular ejection fraction at 48 and 72 h (p ≤ 0.02), and increased urine output and decreased net fluid balance at 72 and 96 h (p ≤ 0.04). AIG also reduced acidosis and renal and hepatic injury markers between 24 and 96 h.ConclusionsThese findings further support AIG’s potential benefit for patients with B. anthracis infection and developing toxin-associated shock.Electronic supplementary materialThe online version of this article (10.1186/s40635-017-0159-9) contains supplementary material, which is available to authorized users.