The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway is a membrane-to-nucleus signaling cascade that effects activation of gene transcription. JAK inhibitors have demonstrated effectiveness in autoimmune diseases such as rheumatoid arthritis. An increased risk of infection, mainly varicella-zoster reactivation, with these new agents is of concern. Comorbid conditions, along with pharmacokinetic variations in drug metabolism in the older population, further increase the risk of adverse outcomes. Newly raised concerns for potential adverse effects such as deep vein thrombosis and pulmonary embolism are essential considerations for clinicians. Older patients are at increased risk because of multiple comorbid conditions and pharmacokinetic changes related to drug metabolism and excretion. Both the US FDA and the European Medicines Agency have issued warnings regarding this risk. These warnings highlight individuals aged > 50 years with concomitant cardiovascular risk factors. Furthermore, the FDA released a black box warning for increased thromboembolic risk associated with JAK inhibitors. As the use of these drugs increases, a solid understanding of adverse effects and risks is critical to those treating older adults. Key Points Thromboembolic risk is an important and emerging consideration for clinicians who prescribe Janus kinase (JAK) inhibitors. Older patients with rheumatoid arthritis are at increased thromboembolic risk because of age and comorbid conditions. The warnings issued by the US FDA and the European Medicines Agency highlight this risk. Infectious complications, such as herpes zoster, are known and essential considerations.

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Introduction Patients with germline variants in CDH1 who undergo prophylactic total gastrectomy (TG) are at risk of altered nutrient and drug absorption due to modified gastrointestinal anatomy. Bone mineral density loss and micronutrient deficiencies have not been described previously in this patient population. Methods In this study we included 94 patients with germline CDH1 variants who underwent prophylactic TG between October 2017 and February 2022. We examined pre- and post-gastrectomy bone mineral density (BMD); serum biomarkers including calcium, phosphorus, alkaline phosphatase, and 25 (OH)-vitamin D; and postoperative adherence to calcium and multivitamin supplementation. Results Almost all patients (92/94, 98%) lost a substantial amount of weight post-TG, with an average weight loss of 26.5% at 12 months post-surgery. Serum biomarkers of mineral metabolism, namely calcium and phosphorus, did not change significantly after TG. However, average BMD was decreased in all patients at 12 months post-TG. Nonadherence to calcium supplementation was associated with a decrease in BMD. Nonadherence to multivitamin supplementation was associated with greater percent BMD loss in the femoral neck and total hip. Conclusions Appropriate micronutrient supplementation and nutritional counseling pre- and postoperatively in patients undergoing prophylactic TG are important to mitigate the long-term effects of gastrectomy on bone health.

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Paecilomyces variotii is an opportunistic mold that causes pulmonary infections in immunosuppressed humans that are often treated with triazole therapy. Lupus nephritis is a major cause of progressive kidney disease in patients with systemic lupus erythematosus, often requiring cyclophosphamide-based therapies. Triazole-cyclophosphamide co-administration is challenging as triazoles increase cyclophosphamide concentrations, which can worsen cyclophosphamide toxicity. We describe herein a patient with Paecilomyces variotii pneumonia and concomitant lupus nephritis who was successfully treated with posaconazole and echinocandin-bridged interruptions to allow for cyclophosphamide therapy. This regimen was well-tolerated without cyclophosphamide toxicity and achieved improvements in both fungal pneumonia and renal function.

Background Vancomycin and β-lactam combinations are used to provide empiric coverage in hospitalized patients. Recent literature has illustrated an increased incidence of nephrotoxicity with such combinations, predominantly with piperacillin-tazobactam and vancomycin. The objective of this study is to evaluate the incidence of nephrotoxicity among patients receiving vancomycin and piperacillin-tazobactam vs., cefepime, or aztreonam. Methods A retrospective, observational, cohort study was conducted at Hahnemann University Hospital in adult patients who received vancomycin plus piperacillin-tazobactam, cefepime, or aztreonam for at least 48 hours between June 2013 and August 2016. Patients were excluded if they had chronic kidney disease Stage III or higher or on continuous renal replacement therapy. The following data were collected: demographics, renal function, number of concomitant nephrotoxic agents, total duration of combination therapy, and vancomycin levels. The primary outcome was the incidence of nephrotoxicity according to the Risk Injury Failure End Stage Renal Disease (RIFLE) criteria. Secondary outcomes were the total length of hospital (LOS) and intensive care unit (ICU) LOS. Statistical analyses were conducted using the Analysis of Variance and the Chi-square test. Results A total of 757 charts were reviewed of which 203 were included in the analysis; 69 in the piperacillin-tazobactam arm, 74 in the cefepime arm, and 60 in the aztreonam arm. The incidence of nephrotoxicity as assessed by the RIFLE criteria was higher in the piperacillin-tazobactam arm (41%) compared with cefepime (15%) and aztreonam arms (17%); P = 0.052. Majority of patients with nephrotoxicity experienced injury according to the RIFLE criteria. No differences were found in the total LOS, ICU LOS, or duration of nephrotoxicity. Patients who experienced nephrotoxicity in the piperacillin-tazobactam arm occurred earlier upon antibiotic initiation at 48 hours compared with the other arms extending past 72 hours; P = 0.004. Conclusion There was a trend towards more patients experiencing nephrotoxicity in the piperacillin-tazobactam arm compared with the other groups. Clinicians should remain vigilant when utilizing combination therapy. Disclosures T. Bias, Merck: Grant Investigator, Research grant. The Medicines Company: Speaker’s Bureau, Speaker honorarium.

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