These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of HSV in the pre‐ and post‐transplant period. A majority of transplant recipients are seropositive for HSV‐1 or 2. Compared with immunocompetent persons, SOT recipients shed HSV more frequently, have more severe clinical manifestations, and are slower to respond to therapy. Most HSV infection is diagnosed on clinical grounds, but patients may present with atypical lesions and/or other clinical manifestations. Acquisition from the donor is rare. Polymerase chain reaction is the preferred diagnostic test unless culture is needed for resistance testing. For limited mucocutaneous lesions, oral therapy can be used; however, in severe, disseminated, visceral or CNS involvement, acyclovir doses of up to 10 mg/kg every 8 hours intravenously should be initiated. Acyclovir‐resistant HSV is less common in SOT patients than in HSCT and can be treated with foscarnet, though other novel therapies are currently under investigation. HSV‐specific prophylaxis should be considered for all HSV‐1 and HSV‐2–seropositive organ recipients who are not receiving antiviral medication for CMV prevention that has activity against HSV.

BackgroundInducible cyclooxgenase-2 (COX-2) is commonly overexpressed in breast tumors and is a target for cancer therapy. Here, we studied the association of COX-2 with breast cancer survival and how this association is influenced by tumor estrogen and HER2 receptor status and Akt pathway activation.MethodsTumor COX-2, HER2 and estrogen receptor α (ER) expression and phosphorylation of Akt, BAD, and caspase-9 were analyzed immunohistochemically in 248 cases of breast cancer. Spearman's correlation and multivariable logistic regression analyses were used to examine the relationship between COX-2 and tumor characteristics. Kaplan-Meier survival and multivariable Cox proportional hazards regression analyses were used to examine the relationship between COX-2 and disease-specific survival.ResultsCOX-2 was significantly associated with breast cancer outcome in ER-negative [Hazard ratio (HR) = 2.72; 95% confidence interval (CI), 1.36-5.41; comparing high versus low COX-2] and HER2 overexpressing breast cancer (HR = 2.84; 95% CI, 1.07-7.52). However, the hazard of poor survival associated with increased COX-2 was highest among patients who were both ER-negative and HER2-positive (HR = 5.95; 95% CI, 1.01-34.9). Notably, COX-2 expression in the ER-negative and HER2-positive tumors correlated significantly with increased phosphorylation of Akt and of the two Akt targets, BAD at Ser136 and caspase-9 at Ser196.ConclusionsUp-regulation of COX-2 in ER-negative and HER2-positive breast tumors is associated with Akt pathway activation and is a marker of poor outcome. The findings suggest that COX-2-specific inhibitors and inhibitors of the Akt pathway may act synergistically as anticancer drugs in the ER-negative and HER2-positive breast cancer subtype.

Objective: The safety and effect of intra-arterial (IA) tirofiban, a glycoprotein IIb/IIIa inhibitor, during the stent retriever mechanical thrombectomy (MT) was investigated. Methods: From January 2015 to May 2019, a total of 327 patients underwent mechanical thrombectomy of large artery occlusions (LAO). Patients were classified into two groups: MT with IA tirofiban (MTT) group and MT only (MTO, without IA tirofiban) group. Clinical outcomes, radiological results, and various complications, such as post thrombectomy hemorrhage, symptomatic hemorrhage, other systemic bleeding, and hemorrhagic transformation of infarct were evaluated by comparing the MTT group and MTO group. In addition, subgroup analysis was performed for patients who underwent MT with prior intravenous (IV) tissue plasminogen activator (t-PA). Results: The MTT group needed a lower mean number of stent passes and showed a re-occlusion rate as compared with the MTO group (P=0.038 and 0.022, respectively). Between the two groups, there were no statistically significant differences in post thrombectomy hemorrhage, symptomatic hemorrhage, other systemic bleeding complications, or hemorrhagic transformation of infarct (P = 0.511, 0.397, 0.429, and 0.355, respectively). In the subgroup analysis, similar findings were observed. Conclusion: The use of IA tirofiban during MT seems to be safe and potentially more effective than only MT without IA tirofiban, even in patients who used IV t-PA before MT.

The extent to which donor multidrug‐resistant organisms (MDROs) affect organ utilization remains unclear. We performed a retrospective cohort study at 4 transplant centers between 2015 and 2016 to evaluate this question. All deceased donors who donated at least one organ were included. Exposed donors had at least one MDRO on culture. Unexposed donors had no MDRO‐positive cultures. Only cultures obtained during the donor's terminal hospitalization were evaluated. Multivariable regression was used to determine the association between donor MDRO and (1) number of organs transplanted per donor and (2) the match run at which each organ was accepted. Subsequently, we restricted the analysis to donors with MDR‐Gram‐negative (GN) organisms. Of 440 total donors, 29 (7%) donors grew MDROs and 7 (2%) grew MDR‐GNs. There was no significant association between donor MDRO and either measure of organ utilization. However, donor MDR‐GNs were associated with a significant reduction in the number of organs transplanted per donor (incidence rate ratio 0.43, 95% confidence interval [CI] 0.39‐0.48, P < .01), and organs were accepted significantly further down the match list (relative count 5.08, 95% CI 1.64‐15.68, P = .01). Though donor MDR‐GNs were infrequent in our study, their growing prevalence could meaningfully reduce the donor pool over time.

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