A Targeted Screening Program for Latent Tuberculosis Infection Among Hematopoietic Cell Transplant Recipients.

BACKGROUND: US hematopoietic cell transplantation (HCT) recipients have a low prevalence of latent tuberculosis infection (LTBI), but if latently infected they are at risk for progression to active tuberculosis. At our center, all HCT recipients underwent LTBI testing pretransplant by tuberculin skin testing (TST) until 2013 when we implemented a targeted screening program. Our objective was to assess the utility of our screening program that incorporated a pretransplant LTBI questionnaire to target TST and QuantiFERON TB Gold (QFT) testing. METHODS: We performed a retrospective cohort study of HCT recipients undergoing first transplant from 2014 to 2016. Patients with positive, indeterminate, and a subset with negative QFT results underwent electronic medical record (EMR) review to assess TST results and risk factors for LTBI. RESULTS: Among 1290 eligible recipients, 457 (35%) had at least 1 risk factor for LTBI on the pretransplant questionnaire; nonwhites were more likely to undergo LTBI testing (P < .0001). Overall, 16 of 1290 (1.2%) had at least 1 positive LTBI test. Of those screened by QFT, 14 of 457 (3%) were positive and 52 (11%) were indeterminate. Among those undergoing EMR review, 123 of 267 (46%) had TST records; 4 of 123 (3%) positive by both TST and QFT, and 2 (2%) by TST alone. Two or more risk factors were reported among the majority of LTBI-positive patients (15 of 16 [94%]). All patients with at least 1 positive test for LTBI (n = 16) were evaluated, and 11 of 16 (69%) were recommended to receive treatment. CONCLUSIONS: Incorporating a pretransplant LTBI questionnaire allowed for an approximate 65% reduction in LTBI testing when compared with universal testing among this low prevalence population.

Using fMRI connectivity to define a treatment-resistant form of post-traumatic stress disorder.

A mechanistic understanding of the pathology of psychiatric disorders has been hampered by extensive heterogeneity in biology, symptoms, and behavior within diagnostic categories that are defined subjectively. We investigated whether leveraging individual differences in information-processing impairments in patients with post-traumatic stress disorder (PTSD) could reveal phenotypes within the disorder. We found that a subgroup of patients with PTSD from two independent cohorts displayed both aberrant functional connectivity within the ventral attention network (VAN) as revealed by functional magnetic resonance imaging (fMRI) neuroimaging and impaired verbal memory on a word list learning task. This combined phenotype was not associated with differences in symptoms or comorbidities, but nonetheless could be used to predict a poor response to psychotherapy, the best-validated treatment for PTSD. Using concurrent focal noninvasive transcranial magnetic stimulation and electroencephalography, we then identified alterations in neural signal flow in the VAN that were evoked by direct stimulation of that network. These alterations were associated with individual differences in functional fMRI connectivity within the VAN. Our findings define specific neurobiological mechanisms in a subgroup of patients with PTSD that could contribute to the poor response to psychotherapy.

Selective Effects of Psychotherapy on Frontopolar Cortical Function in PTSD.

OBJECTIVE: Exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD), but a comprehensive, emotion-focused perspective on how psychotherapy affects brain function is lacking. The authors assessed changes in brain function after prolonged exposure therapy across three emotional reactivity and regulation paradigms. METHOD: Individuals with PTSD underwent functional MRI (fMRI) at rest and while completing three tasks assessing emotional reactivity and regulation. Individuals were then randomly assigned to immediate prolonged exposure treatment (N=36) or a waiting list condition (N=30) and underwent a second scan approximately 4 weeks after the last treatment session or a comparable waiting period, respectively. RESULTS: Treatment-specific changes were observed only during cognitive reappraisal of negative images. Psychotherapy increased lateral frontopolar cortex activity and connectivity with the ventromedial prefrontal cortex/ventral striatum. Greater increases in frontopolar activation were associated with improvement in hyperarousal symptoms and psychological well-being. The frontopolar cortex also displayed a greater variety of temporal resting-state signal pattern changes after treatment. Concurrent transcranial magnetic stimulation and fMRI in healthy participants demonstrated that the lateral frontopolar cortex exerts downstream influence on the ventromedial prefrontal cortex/ventral striatum. CONCLUSIONS: Changes in frontopolar function during deliberate regulation of negative affect is one key mechanism of adaptive psychotherapeutic change in PTSD. Given that frontopolar connectivity with ventromedial regions during emotion regulation is enhanced by psychotherapy and that the frontopolar cortex exerts downstream influence on ventromedial regions in healthy individuals, these findings inform a novel conceptualization of how psychotherapy works, and they identify a promising target for stimulation-based therapeutics.