Objective: Heightened generalization of fear from an aversively reinforced conditioned stimulus (CS+, a conditioned danger cue) to resembling stimuli is widely accepted as a pathogenic marker of posttraumatic stress disorder (PTSD). Indeed, a distress response to benign stimuli that "resemble" aspects of the trauma is a central feature of the disorder. To date, the link between overgeneralization of conditioned fear and PTSD derives largely from clinical observations, with limited empirical work on the subject. This represents the first effort to examine behavioral and brain indices of generalized conditioned fear in PTSD using systematic methods developed in animals known as generalization gradients: the gradual decline in conditioned responding as the presented stimulus gradually differentiates from CS+.Method: Gradients of conditioned fear generalization were assessed using functional MRI and behavioral measures in U.S. combat veterans who served in Iraq or Afghanistan and had PTSD (N=26), subthreshold PTSD (N=19), or no PTSD (referred to as trauma control subjects) (N=17). Presented stimuli included rings of graded size, with extreme sizes serving as CS+ (paired with shock) and as a nonreinforced conditioned stimulus (CS-, a conditioned safety cue), and with intermediate sizes forming a continuum of similarity between CS+ and CS-. Generalization gradients were assessed as response slopes from CS+, through intermediate ring sizes, to CS-, with less steep slopes indicative of stronger generalization.Results: Relative to trauma control subjects, PTSD patients showed stronger conditioned generalization, as evidenced by less steep generalization gradients in both behavioral risk ratings and brain responses in the left and right anterior insula, left ventral hippocampus, dorsolateral and dorsomedial prefrontal cortex, and caudate nucleus. Severity of PTSD symptoms across the three study groups was positively correlated with levels of generalization at two such loci: the right anterior insula and left ventral hippocampus. Conclusions:The results point to evidence of brain-based markers of overgeneralized fear conditioning related to PTSD. These findings provide further understanding of a central yet understudied symptom of trauma-related psychopathology. Am J Psychiatry 2017; 174:125-134; doi: 10.1176/appi.ajp.2016 Generalization of conditioned fear is a basic, cross-species, associative-learning process whereby fear acquired to a conditioned stimulus (CS+), paired with an aversive unconditioned stimulus, transfers to safe stimuli resembling the CS+ (1). Heightened levels of generalized conditioned fear have been adopted as a core feature of trauma-related psychopathology (2), and DSM-5 criteria for posttraumatic stress disorder (PTSD) include heightened distress to situations "resembling" aspects of the trauma. The pathogenic contribution of conditioned generalization to PTSD follows from the undue proliferation of trauma cues in an individual's posttrauma environment that then increases and/or sustains PTSD sympt...

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Combined heart-kidney transplantation (CHKT) is a therapy for a carefully selected subgroup of patients with concomitant heart and kidney failure. Discerning whether there is reversible or irreversible kidney disease is crucial to selection for CHKT versus heart transplant alone to optimize therapeutic value and organ allocation. Methods for determining extent of kidney disease include estimating glomerular filtration rate, creatinine clearance, kidney ultrasonography, and kidney biopsy. Additionally, the use of extracorporeal membrane oxygenation (ECMO) in the setting of CHKT only recently emerged as feasible. We present a case of a 69-year-old man with cardiogenic shock who was placed on venoarterial-ECMO (VA-ECMO) following orthotopic heart transplant (OHT) due to severe mediastinal bleeding and remained on VA-ECMO during kidney transplant. To our knowledge, this is the second report of a patient undergoing kidney transplant while on VA-ECMO following OHT.

Background: Kidney transplant recipients are at increased risk of severe disease and death caused by coronavirus disease 2019 (COVID-19) infection. The role of immunosuppressive medications in the clinical presentation, disease course, and outcomes is not well understood. Methods: We analyzed kidney transplant recipients diagnosed with COVID-19 and requiring hospitalization during the initial infection surge at 2 large transplant centers in New Orleans, Louisiana, between February 1, 2020 and April 30, 2020. Patient presentation, clinical course, kidney transplant function, and postdischarge details are included in this analysis. Results: Twenty-three kidney transplant recipients hospitalized with COVID-19 were included in the study. The majority of patients were Black (95.7%). Diabetes, hypertension, and obesity were present in more than 50% of the patients. The most common presenting symptom was fever, present in 52.2% of patients. All patients were managed with reduction in immunosuppression. Patients received azithromycin (60.9%), hydroxychloroquine (47.8%), remdesivir (8.7%), and intravenous methylprednisolone pulse (8.7%). The average length of stay was 4.5 days (range, 2-18 days). In this study population, 73.9% of the patients sustained acute kidney injury, with an average peak serum creatinine of 3.81 mg/dL. Twenty-six percent of the patients required renal replacement therapy. Seventy-seven percent of patients developed proteinuria (at least 1+ proteinuria on urinalysis). Of the patients in this population who required mechanical ventilation (39.1%), 77.8% died. Overall, 30.4% of patients died of COVID-19–related complications during admission. Of the 16 patients discharged, the average serum creatinine at discharge was 2.09 mg/dL compared with an average preadmission serum creatinine of 1.8 mg/dL. Conclusion: During the initial COVID-19 infection surge in New Orleans, we noted that kidney transplant recipients had initial symptoms similar to the general population. However, we recorded a higher incidence of acute kidney injury and death compared to nontransplant patients. Patients who required mechanical ventilation had a high mortality rate. Black patients are overrepresented in our study.

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