Cefepime challenge after piperacillin/tazobactam-induced thrombocytopenia.

Drug-induced thrombocytopenia (DITP) has been described as a sudden and severe hematologic complication of piperacillin/tazobactam. The proposed mechanism by which piperacillin/tazobactam causes DITP involves the formation of a covalent bond to platelet membrane protein thereby inducing a humoral immune response. Given the immunogenic nature of this adverse event and the structural similarities across beta-lactam antibiotics, the potential for cross-reactivity between agents within the class should be considered. However, the structural moiety of piperacillin/tazobactam responsible for this immunogenic response has not been identified-the relationship between structure and activity for this phenomenon remains unknown. Data on the safety and cross-reactivity of other beta-lactam agents in this setting is lacking. We report the first case of piperacillin/tazobactam DITP successfully challenged by the use of cefepime for the treatment of aspiration pneumonia. Further studies are needed to determine the structural moiety of piperacillin/tazobactam responsible for this immunogenic response and evaluate the safety of other beta-lactam antibiotics in this clinical setting.

Characterization of the Effect of Prolonged Therapeutic Hypothermia on Serum Magnesium and Potassium Following Neurological Injury.

Current American Heart Association/American Stroke Association guidelines for the management of spontaneous intracerebral hemorrhage suggest therapeutic hypothermia (TH) as a salvage therapy in patients with elevated intracranial pressure. Electrolyte disorders may develop at any stage of the cooling process. Such deregulation can place patients at an increased risk for arrhythmias and worsened neurologic outcomes. The impact of TH on serum electrolyte concentration has been described, but electrolyte changes and repletions are yet to be quantified. The primary objective of this study was to quantify the trends in serum potassium and magnesium concentrations during TH and determine the median amount of electrolyte repletions administered. This study was a single-center retrospective cohort conducted at Virginia Commonwealth University Health. Data were collected from neurosurgical patients with intracranial hypertension who underwent TH (<36°C) for ≥48 hours. Patients with a primary neurological insult cooled with the Arctic Sun® 5000 Temperature Management System, who were ≥13 years of age at the time of therapy with a core body temperature of ≥36°C before therapeutic hypothermia, were eligible for inclusion. Forty-three patients meeting the inclusion criteria were analyzed. A total of 42 patients (98%) experienced hypokalemia (<3.5 mEq/L) during TH. A median of 45 mEq per day of potassium repletion was administered during the maintenance phase of cooling. Despite those repletions, patients remained hypokalemic 30% of the time. Median serum magnesium concentrations during the maintenance phase of TH remained consistently within goal range of 1.8-2.5 mg/dL. Five patients (12%) experienced at least one episode of cardiac dysrhythmia during the cooling period. Standard potassium electrolyte repletion protocols did not adequately maintain serum potassium concentrations above our target of 3.5 mEq/L in neurosurgical patients undergoing TH. Standard magnesium repletion protocols were sufficient to maintain a normal serum concentration in this patient population when magnesium sulfate was not used for other indications.

Bookkeeping of insect herbivory trends in herbarium specimens of purple loosestrife (Lythrum salicaria).

The potential use of herbarium specimens to detect herbivory trends is enormous but largely untapped. The objective of this study was to reconstruct the long-term herbivory pressure on the Eurasian invasive plant, purple loosestrife (Lythrum salicaria), by evaluating leaf damage over 1323 specimens from southern Québec (Canada). The hypothesis tested is that that the prevalence of herbivory damage on purple loosestrife is low during the invasion phase and increases throughout the saturation phase. Historical trends suggest a gradual increase in hole feeding and margin feeding damage from 1883 to around 1940, followed by a period of relative stability. The percentage of specimens with window feeding damage did not begin to increase until the end of the twentieth century, from 3% (2-6%) in 1990 to 45% (14-81%) in 2015. Temporal changes in the frequency of window feeding damage support the hypothesis of an increasing herbivory pressure by recently introduced insects. This study shows that leaf damage made by insects introduced for the biocontrol of purple loosestrife, such as coleopterans of the Neogalerucella genus, can be assessed from voucher specimens. Herbaria are a rich source in information that can be used to answer questions related to plant-insect interactions in the context of biological invasions and biodiversity changes.This article is part of the theme issue 'Biological collections for understanding biodiversity in the Anthropocene'.

Talimogene Laherparepvec: An Oncolytic Virus Therapy for Melanoma.

OBJECTIVE: To review the efficacy and safety of talimogene laherparepvec (T-VEC) as well as its pharmacology, pharmacokinetics, drug-drug interactions, handling procedures, cost considerations, and place in therapy. DATA SOURCES: Searches of PubMed (1966 to February 2017) and Cochrane Library (1999 to February 2017) were conducted using the terms talimogene laherparepvec, T-VEC, OncoVEX, immunotherapy, melanoma, and oncolytic virus. Additional information was determined from bibliographies, manufacturer product labeling and website, meeting abstracts, Food and Drug Administration website, and clinicaltrials.gov. STUDY SELECTION AND DATA EXTRACTION: A total of 79 English-language publications were identified. Articles that assessed T-VEC's pharmacokinetics, pharmacodynamics, mechanism, dosing, safety, and efficacy were included as well as narrative reviews that provided practical information. DATA SYNTHESIS: Clinical trials have confirmed the safety and efficacy of T-VEC as monotherapy for the treatment of advanced melanoma, with an overall response rate (ORR) of 26%. Relative to granulocyte-macrophage colony-stimulating factor, T-VEC significantly increased durable response rate (DRR; 16.3% vs 2.1%, P < 0.001); however, median overall survival was not improved (23.3 vs 18.9 months, P = 0.051). Phase 1b trials have combined T-VEC and immunotherapies with promising results. T-VEC's adverse effects are generally considered mild to moderate in severity. CONCLUSION: T-VEC is the first approved oncolytic virus for local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in melanoma recurrent after initial surgery. T-VEC improves ORR and DRR as a single agent, shows promise in combination therapy, and is well tolerated. Ongoing trials will determine if T-VEC has a role in early treatment or in combination therapy for melanoma or other malignancies.