Active coping, resilience, post-traumatic growth, and psychiatric symptoms among early and late liver transplant survivors.

Understanding survivorship experiences at different stages postliver transplantation (poat-LT) is essential to improving care. Patient-reported concepts including coping, resilience, post-traumatic growth (PTG), and anxiety/depression, have been implicated as important predictors of quality of life and health behaviors after LT. We aimed to descriptively characterize these concepts at different post-LT survivorship stages. This cross-sectional study featured self-reported surveys measuring sociodemographic, clinical characteristics, and patient-reported concepts including coping, resilience, PTG, anxiety, and depression. Survivorship periods were categorized as early (1 y or below), mid (1-5 y), late (5-10 y), and advanced (10 y or above). Univariable and multivariable logistic and linear regression modeling examined factors associated with patient-reported concepts. Among 191 adult LT survivors, the median survivorship stage was 7.7 years (interquartile range: 3.1-14.4) and median age was 63 years (range: 28-83); most were male (64.2%) and Caucasian (84.0%). High PTG was more prevalent in the early survivorship period (85.0%) than late survivorship (15.2%). High trait resilience was only reported by 33% of survivors and associated with higher income. Lower resilience was seen among patients with longer LT hospitalization stays and late survivorship stages. About 25% of survivors had clinically significant anxiety and depression, which was more frequent among early survivors and females with pre-LT mental health disorders. In multivariable analysis, factors associated with lower active coping included survivors ≥65 years, non-Caucasian race, lower levels of education, and nonviral liver disease. In a heterogeneous cohort including early and late LT survivors, there was variation in levels of PTG, resilience, anxiety, and depression at different survivorship stages. Factors associated with positive psychological traits were identified. Understanding determinants of LT survivorship has important implications for how we should monitor and support LT survivors.

Post-Traumatic Stress Disorder and Post-Traumatic Growth following Kidney Transplantation.

Background: Kidney transplantation (KT) is a life-saving therapy for kidney failure. However, KT recipients can suffer from debilitating depression, post-traumatic stress disorder (PTSD), and suicide. In contrast to PTSD, post-traumatic growth (PTG) is a positive psychologic change in response to a challenging situation. PTG has been studied in other chronic diseases, but less is known about its role in the setting of KT. We sought to elucidate the prevalence, predictors, and the effect of PTSD and PTG on post-KT outcomes. We also considered the roles of benefit finding and resilience. Methods: In a literature review, we identified publications that examined PTSD, PTG, benefit finding, and/or resilience in KT recipients. We excluded case reports and first-person narratives. Publications meeting the specified criteria after full text review underwent data abstraction and descriptive analysis. Results: Of the 1013 unique citations identified, 39 publications met our criteria. PTSD was the most common construct evaluated (16 publications). Resilience was studied in 11 publications, PTG in nine, and benefit finding in five. Up to 21% of adult and 42% of pediatric KT recipients may experience PTSD, which is associated with lower quality of life (QOL), impaired sleep, and other psychiatric comorbidity. PTG was associated with improved QOL, kidney function, and reduced risk of organ rejection. Although benefit finding tended to increase post KT, resilience remained stable post KT. Like PTG, resilience was associated with lower psychologic distress and increased treatment adherence and confidence in the health care team. Conclusions: PTG, resilience, and benefit finding appear to reduce the risk of PTSD, promote well-being, and reduce risk of graft failure in KT recipients. Future research to understand these relationships better will allow clinicians and researchers to develop interventions to promote PTG, resilience, and benefit finding, and potentially improve post-transplant outcomes such as adherence and reducing risk of organ rejection.

Implementation of a Psychiatry Consultation-Liaison Service "Conseminar".

BACKGROUND: The field of consultation-liaison psychiatry has generated a relatively small number of rigorous clinical trials that guide clinical care. Consequently, there is a need for a consensus-building process to inform best practices for common clinical dilemmas in consultation-liaison psychiatry. OBJECTIVE: We review several consensus-building approaches in academic medicine and describe a novel educational process called a "conseminar," which is intended to minimize the variability in teaching and practice on a service staffed by multiple faculty members. METHODS: The conseminar is an iterative group exercise among faculty who attend on a consultation-liaison service. Faculty members generate a list of candidate topics and then prioritize those topics for a focused and critical literature review, aided by a librarian. In the absence of definitive clinical trial data or established practice guidelines, the faculty articulates a consensus "best-practice" approach and creates a brief document that summarizes specific recommendations for learners on the service. CONCLUSIONS: The conseminar process can minimize variability among consultation-liaison faculty within a single institution with respect to the diagnostic and treatment recommendations conveyed to trainees. Furthermore, conseminar documents can be shared across institutions to promote more consistent teaching and practice within consultation-liaison psychiatry.

Neuropsychiatric Complications of COVID-19.

PURPOSE OF REVIEW: To describe the presentation, etiologies, and suggested management of post-acute COVID-19 neuropsychiatric symptoms. RECENT FINDINGS: Over 30% of patients hospitalized with COVID-19 may exhibit cognitive impairment, depression, and anxiety that persist for months after discharge. These symptoms are even more common in patients who required intensive care for severe effects of the virus. In addition to the pandemic-related psychological stress, multiple biological mechanisms have been proposed to understand the neuropsychiatric symptoms observed with COVID-19. Given limited research regarding effective interventions, we recommend pharmacologic and behavioral strategies with established evidence in other medically-ill populations. Long-term, neuropsychiatric complications of COVID-19 are common and consequential. Because these are likely to co-occur with other medical problems, patients recovering from COVID-19 are best managed in clinics with highly coordinated care across disciplines and medical specialties. Future research is needed to inform appropriate interventions.

Psychiatric Care in Hematopoietic Stem Cell Transplantation.

BACKGROUND: Patients with cancer frequently experience neuropsychiatric symptoms due to their medical illness or its treatment. In recent decades, psychiatrists have become increasingly involved in the care of patients with cancer. However, psychiatrists may be less familiar with hematopoietic stem cell transplantation (HSCT), a distinct cancer treatment modality associated with multiple neuropsychiatric sequelae. OBJECTIVE: To provide an overview of HSCT, and describe the prevalence, impact, risk factors, and suggested management of psychiatric consequences of HSCT. METHODS: We performed literature searches in PubMed and PsychInfo to identify articles describing neuropsychiatric symptoms, including depression, anxiety, distress, post-traumatic stress disorder, delirium and cognitive impairment, resulting from HSCT in adults. Those articles most relevant to this manuscript were included. RESULTS: Psychiatrists may be involved in the treatment of patients before, during, or after inpatient hospitalization for HSCT. Each phase of treatment introduces unique stressors that may lead to or exacerbate psychiatric disorders. Appropriate management requires evaluation of HSCT-related medications, an understanding of the impact of complications from HSCT, and consideration of how the patient's underlying medical condition should influence psychiatric recommendations. CONCLUSION: To optimize patient outcomes, consulting psychiatrists should be familiar with the basic principles of HSCT, and the neuropsychiatric sequelae that may result from treatment. Further research is needed to identify strategies to manage psychiatric complications in this unique population.

Acute Pharmacological Management of Behavioral and Emotional Dysregulation Following a Traumatic Brain Injury: A Systematic Review of the Literature.

BACKGROUND: Traumatic brain injury (TBI) is an increasingly common cause of behavioral and emotional dysregulation among hospitalized patients. While consultation-liaison psychiatrists are often called to help manage these behaviors, acute pharmacological management guidelines are limited. OBJECTIVE: Conduct a systematic review to determine which pharmacological measures are supported by the literature for targeting agitation and aggression in the acute time period following a TBI. METHODS: In a systematic review of MEDLINE, Embase, PsycInfo, ClinicalTrials.gov and the Cochrane Library, we identified and then analyzed publications that investigated the pharmacological management of behavioral and emotional dysregulation following a TBI during the acute time period following injury. RESULTS: There were a limited number of high quality studies that met our inclusion criteria, including only five randomized controlled trials. The majority of the literature identified consisted of case reports or case series. Trends identified in the literature reviewed suggested that amantadine, propranolol, and anti-epileptics were the best supported medications to consider. For many medication classes, the time of medication initiation and duration of treatment, relative to the time of injury, may impact the effect observed. CONCLUSIONS: The pharmacological management of agitated patients immediately following a TBI is still an area of much-needed research, as there is limited data-driven guidance in the literature.

Unique helicase determinants in the essential conjugative TraI factor from Salmonella enterica serovar Typhimurium plasmid pCU1.

The widespread development of multidrug-resistant bacteria is a major health emergency. Conjugative DNA plasmids, which harbor a wide range of antibiotic resistance genes, also encode the protein factors necessary to orchestrate the propagation of plasmid DNA between bacterial cells through conjugative transfer. Successful conjugative DNA transfer depends on key catalytic components to nick one strand of the duplex DNA plasmid and separate the DNA strands while cell-to-cell transfer occurs. The TraI protein from the conjugative Salmonella plasmid pCU1 fulfills these key catalytic roles, as it contains both single-stranded DNA-nicking relaxase and ATP-dependent helicase domains within a single, 1,078-residue polypeptide. In this work, we unraveled the helicase determinants of Salmonella pCU1 TraI through DNA binding, ATPase, and DNA strand separation assays. TraI binds DNA substrates with high affinity in a manner influenced by nucleic acid length and the presence of a DNA hairpin structure adjacent to the nick site. TraI selectively hydrolyzes ATP, and mutations in conserved helicase motifs eliminate ATPase activity. Surprisingly, the absence of a relatively short (144-residue) domain at the extreme C terminus of the protein severely diminishes ATP-dependent strand separation. Collectively, these data define the helicase motifs of the conjugative factor TraI from Salmonella pCU1 and reveal a previously uncharacterized C-terminal functional domain that uncouples ATP hydrolysis from strand separation activity.

Investigating the impact of bisphosphonates and structurally related compounds on bacteria containing conjugative plasmids.

Bacterial plasmids propagate through microbial populations via the directed process of conjugative plasmid transfer (CPT). Because conjugative plasmids often encode antibiotic resistance genes and virulence factors, several approaches to inhibit CPT have been described. Bisphosphonates and structurally related compounds (BSRCs) were previously reported to disrupt conjugative transfer of the F (fertility) plasmid in Escherichia coli. We have further investigated the effect of these compounds on the transfer of two additional conjugative plasmids, pCU1 and R100, between E. coli cells. The impact of BSRCs on E. coli survival and plasmid transfer was found to be dependent on the plasmid type, the length of time the E. coli were exposed to the compounds, and the ratio of plasmid donor to plasmid recipient cells. Therefore, these data indicate that BSRCs produce a range of effects on the conjugative transfer of bacterial plasmids in E. coli. Since their impact appears to be plasmid type-dependent, BSRCs are unlikely to be applicable as broad inhibitors of antibiotic resistance propagation.

Tyrosine partners coordinate DNA nicking by the Salmonella typhimurium plasmid pCU1 relaxase enzyme.

Conjugative plasmid transfer results in the spread of antibiotic resistance genes and virulence factors between bacterial cells. Plasmid transfer is dependent upon the DNA nicking activity of a plasmid-encoded relaxase enzyme. Tyrosine residues within the relaxase cleave the DNA plasmid nic site in a highly sequence-specific manner. The conjugative resistance plasmid pCU1 encodes a relaxase with four tyrosine residues surrounding its active site (Y18,19,26,27). We use activity assays to demonstrate that the pCU1 relaxase preferentially uses Y26 or a combination of Y18 + 19 to nick DNA at wild type levels, and that an adjacent aspartic acid deprotonates these tyrosines to activate them for attack. Our findings illustrate the unique modifications that the pCU1 relaxase has introduced into the traditional relaxase-mediated DNA nicking mechanism.

Functional characterization of the multidomain F plasmid TraI relaxase-helicase.

TraI, a bifunctional enzyme containing relaxase and helicase activities, initiates and drives the conjugative transfer of the Escherichia coli F plasmid. Here, we examined the structure and function of the TraI helicase. We show that TraI binds to single-stranded DNA (ssDNA) with a site size of ∼25 nucleotides, which is significantly longer than the site size of other known superfamily I helicases. Low cooperativity was observed with the binding of TraI to ssDNA, and a double-stranded DNA-binding site was identified within the N-terminal region of TraI 1-858, outside the core helicase motifs of TraI. We have revealed that the affinity of TraI for DNA is negatively correlated with the ionic strength of the solution. The binding of AMPPNP or ADP results in a 3-fold increase in the affinity of TraI for ssDNA. Moreover, TraI prefers to bind ssDNA oligomers containing a single type of base. Finally, we elucidated the solution structure of TraI using small angle x-ray scattering. TraI exhibits an ellipsoidal shape in solution with four domains aligning along one axis. Taken together, these data result in the assembly of a model for the multidomain helicase activity of TraI.