BackgroundAfter 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.MethodsWe 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.ResultsAfter 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.ConclusionsGM-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.

Whether implanted as bridge-to-transplantation therapy or destination-therapy, left ventricular assist devices (LVADs) continue to occupy an important niche in the management of advanced heart failure. 1 The majority of the 24,000 devices registered in the Interagency Registry of Mechanically Assisted Circulatory Support database are continuous-flow (CF) LVADs, 2 and long-term use of LVADs in appropriate patient populations has been demonstrated to both improve quality of life and offer a survival benefit. 3 Complications following device placement are well known and include stroke, pump thrombosis, and infection. 4 As implanted foreign bodies, LVADs serve as a nidus for infection, 1 and infections have been common in multiple studies conducted in several countries. 5-7

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.

Patients with focal temporal lobe seizures often experience loss of consciousness. In humans, this loss of consciousness has been shown to be positively correlated with EEG neocortical slow waves, similar to those seen in non-REM sleep. Previous work in rat models of temporal lobe seizures suggests that decreased activity of subcortical arousal systems cause depressed cortical function during seizures. However, these studies were performed under light anesthesia, making it impossible to correlate behavior, and therefore consciousness, to electrophysiologic data. Further, the genetic and molecular toolkits allowing for precise study of the underlying neural circuitry are much more developed in mice than in rats. Here, we describe an awake-behaving, head-fixed mouse model of temporal lobe seizures with both spared and impaired behavior reflecting level of consciousness. Water-restricted mice were head-fixed on a running wheel and trained to associate an auditory stimulus to the delivery of a drop of water from a dispenser. To investigate the effect of seizures on behavior, seizures were electrically induced by stimulating either the left or right hippocampus via a chronically-implanted electrode, while mice were performing the task. Behavior was measured by monitoring lick responses to the auditory stimulus and running speed on the wheel. Further, local field potentials (LFP) signals were simultaneously recorded from hippocampus and orbitofrontal cortex (OFC). Induced focal seizures were 5-30s in duration, and repeatable for several weeks (n=20 animals). Behavioral responses showed a decrease in lick rate to auditory stimulus, and decreased running speed during seizures (p<0.01, n=20 animals). Interestingly, licking response to sound could vary from being impaired to normal during seizures. We found that behavioral impairment is correlated with large amplitude cortical slow-wave activity in frontal cortex, as seen in patients with temporal lobe seizures. These results suggest that induced focal limbic seizures in the mouse can impair consciousness and that the impaired consciousness is correlated with depressed cortical function resembling slow wave sleep. This novel mouse model has similar characteristics with previously studied rat models and human temporal lobe seizures. By leveraging the genetic and molecular techniques available in the mouse, this model can be used to further uncover fundamental mechanisms for loss of consciousness in focal seizures.

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. K E Y W O R D S clinical review, transplant 1 | INTRODUCTION The number of heart donors is insufficient to meet demand and the role of left ventricular assist devices (LVADs) continues to expand in the treatment of medically refractory heart failure. 1 Infections frequently complicate the clinical courses of patients with LVADs and percutaneous driveline infections (DLIs) are the most common type. 2 Staphylococcal spp. and Gram-negative bacteria cause most DLIs, 3 but DLIs caused by nontuberculous mycobacterial (NTM) species have recently been reported. 4-7 We present the second-ever reported case of a DLI caused by Mycobacterium fortuitum in a 75-year-old male with a continuous-flow LVAD. After receiving triple antimycobacterial coverage, he underwent device exchange and ultimately died after failing to recover neurologically. To better understand NTM infections in LVAD patients, we performed a comprehensive literature review and summarized all reported cases. 2 | MATERIALS AND METHODS Between 2007 and 2019, our institution performed over 200 LVAD placement procedures. The following case represents the only documented M. fortuitum infection. Our retrospective review of medical records was approved by the Institutional Review Board of Yale University. | RESULTSA 75-year-old male with atrial fibrillation, ventricular tachycardia, and ischemic cardiomyopathy status post biventricular implanted cardioverter defibrillator and HeartMate II (HM2; Abbott Laboratories) device placement (28 months prior as destination therapy) presented to the emergency department with blood-tinged, purulent drainage from the driveline exit site associated with a 10-cm bacterium chimaera were also afebrile upon initial presentation. [4][5][6] Both M. chimaera cases lacked leukocytosis, similar to our case. 6 Only the Mycobacterium intracellulare case is reported to have had mild fever (37.7°C) upon presentation, and disseminated disease was later confirmed with positive culture results and imaging studies. 8 This case is notable in our series for not being attributable to LVAD har...