Arginase-1 Is Required for Macrophage-Mediated Renal Tubule Regeneration.

BACKGROUND: After kidney injury, macrophages transition from initial proinflammatory activation to a proreparative phenotype characterized by expression of arginase-1 (Arg1), mannose receptor 1 (Mrc1), and macrophage scavenger receptor 1 (Msr1). The mechanism by which these alternatively activated macrophages promote repair is unknown. METHODS: We characterized the macrophage and renal responses after ischemia-reperfusion injury with contralateral nephrectomy in LysM-Cre;Arg1fl/fl mice and littermate controls and used in vitro coculture of macrophages and tubular cells to determine how macrophage-expressed arginase-1 promotes kidney repair. RESULTS: After ischemia-reperfusion injury with contralateral nephrectomy, Arg1-expressing macrophages were almost exclusively located in the outer stripe of the medulla adjacent to injured S3 tubule segments containing luminal debris or casts. Macrophage Arg1 expression was reduced by more than 90% in injured LysM-Cre;Arg1fl/fl mice, resulting in decreased mouse survival, decreased renal tubular cell proliferation and decreased renal repair compared with littermate controls. In vitro studies demonstrate that tubular cells exposed apically to dead cell debris secrete high levels of GM-CSF and induce reparative macrophage activation, with those macrophages in turn secreting Arg1-dependent factor(s) that directly stimulate tubular cell proliferation. CONCLUSIONS: GM-CSF-induced, proreparative macrophages express arginase-1, which is required for the S3 tubular cell proliferative response that promotes renal repair after ischemia-reperfusion injury.

Bordetella bronchiseptica: a rare cause of meningitis.

BACKGROUND: Bordetella bronchiseptica is a gram-negative, obligate aerobic coccobacillus known to cause disease in domesticated animals and pets. In humans, B. bronchiseptica commonly leads to respiratory infections like pneumonia or bronchitis, and animal contact usually precedes the onset of symptoms. CASE PRESENTATION: We report a case of post-traumatic B. bronchiseptica meningitis without recent surgery in the setting of immunosuppression with a monoclonal antibody. Our case concerns a 77-year-old male with ulcerative colitis on infliximab who sustained a mechanical fall and developed a traumatic cerebrospinal fluid leak complicated by meningitis. He received meropenem then ceftazidime during his hospital course, and temporary neurosurgical drain placement was required. His clinical condition improved, and he was discharged at his baseline neurological status. CONCLUSIONS: B. bronchiseptica is an unusual cause of meningitis that may warrant consideration in immunocompromised hosts with known or suspected animal exposures. To better characterize this rare cause of meningitis, we performed a systematic literature review and summarized all previously reported cases.

Efficacy and safety of chronic antimicrobial suppression therapy for left ventricular assist device driveline infections: A single-center descriptive experience.

BACKGROUND: Driveline infection (DLI) is the most common left ventricular assist device (LVAD) infectious complication. Short-term antimicrobial therapy and local debridement are the cornerstones of management for these infections, but the use of chronic antimicrobial suppression (CAS) therapy is not well characterized. METHODS: To better characterize the efficacy of CAS therapy, we performed a retrospective review of all patients (N = 219) receiving care at our tertiary transplant center with continuous-flow LVADs placed between August 2007 and July 2019. RESULTS: A total of 24 patients were identified as having received CAS therapy as treatment for DLIs. The mean age was 56 years, 50% were female, and chronic kidney disease affected 63% of patients. Staphylococcus aureus accounted for half of all initial DLIs, and the mean length of CAS therapy was 486 days (range 48-2287 days). All patients received per os regimens as suppression therapy. Adverse events impacted 5 of 24 patients (0.43 events per 1000 days). Overall, the use of CAS therapy led to successful outcomes in 50% of patients and 29% experienced treatment failures. The remaining patients experienced stable symptoms. Relapses were the most common cause of treatment failure, and three patients experienced reinfections while on CAS therapy. CONCLUSIONS: Our study suggests that CAS therapy for DLIs can be well tolerated, and future studies are needed to determine which patients merit suppression.

Nontuberculous mycobacterial infections in left ventricular assist device patients.

Left ventricular assist devices (LVADs) are integral for the management of medically refractory heart failure, and LVAD infections are common following device placement. Most infections are caused by Staphylococcal spp. and Gram-negative enteric bacteria but nontuberculous mycobacterial (NTM) infections have been reported. We present the second-ever reported case of a driveline infection caused by Mycobacterium fortuitum in a 75-year-old male with a continuous-flow LVAD. After receiving meropenem, azithromycin, and ciprofloxacin, he underwent device exchange and ultimately died after failing to recover neurologically. Management of NTM infections presents a clinical challenge due to the propensity for rapidly growing mycobacterial species to form biofilms and the possibility of negative cultures delaying diagnosis. To address the literature gap surrounding NTM infections in LVAD patients, we performed a systematic review and present all previously reported cases.