Characteristics and Outcomes Among U.S. Commercially Insured Transgender Adults with Cirrhosis: A National Cohort Study.

OBJECTIVE: The National Institute on Minority Health and Health Disparities has noted that transgender individuals experience unique health disparities. We sought to describe the landscape of transgender patients with cirrhosis. METHODS: We identified all trans- and cis-gender adults in Optum's de-identified Clinformatics® Data Mart Database between 2007-2022 using validated billing codes, calculating age-standardized prevalence of cirrhosis among cis- vs. transgender adults. Among those with incident cirrhosis diagnoses, we calculated age-standardized incidence densities of liver-related outcomes (decompensation, transplantation, hepatocellular carcinoma), and all-cause mortality. We examined 5-year survival using inverse probability treatment weighting (IPTW) to balance trans- and cis-gender populations on demographic and clinical characteristics. RESULTS: Among 64,615,316 adults, 42,471 (0.07%) were transgender. Among 329,251 adults with cirrhosis, 293 (0.09%) were transgender. Trans- (vs cis-)genders had higher prevalence of cirrhosis (1,285[95%CI 1,136-1,449] per 100,000 vs 561[559-563] per 100,000). Among adults with cirrhosis, trans- (vs cis-)genders had higher proportions of anxiety (70.7%[56.9-86.9] vs 43.2%[42.7-43.8]), depression (66.4%[53.3-81.7] vs 38.4%[37.9-38.9]), HIV/AIDS (8.5%[3.9-16.1] vs 1.6%[1.5-1.7]), and alcohol (57.5%[46.0-71.1] vs 51.0%[50.5-51.6]) and viral (30.5%[22.8-39.8] vs 24.2%[23.9-24.5]) etiologies, although etiologies had overlapping confidence intervals. Trans- (vs cis-)genders had similar incidence densities of death (12.0[95%CI 8.8-15.3] vs 14.0[13.9-14.2] per 100 person-years), decompensation (15.7[10.9-20.5] vs 14.1[14.0-14.3]), and liver transplantation (0.3[0.0-0.8] vs 0.3[0.3-0.4]). In IPTW survival analysis, trans- and cis-gender individuals had similar 5-year survival probabilities (63.4%[56.6-71.1] vs 59.1%[58.7-59.4]). CONCLUSIONS: Trans- (vs cis-)gender adults have double the prevalence of cirrhosis and the majority have a diagnosis of anxiety and/or depression. These results are informative for researchers, policymakers, and clinicians to advance equitable care for transgender individuals.

Benign to Malignant Hepatic Lesion Transformation in Abernethy Malformation.

Abernethy malformation or congenital extrahepatic portosystemic shunt is an extremely rare condition whereby the portomesenteric blood drains into a systemic vein and bypasses the liver through a complete or partial shunt. Severe complications include hyperammonemia and encephalopathy, benign and malignant liver tumors, and hepatopulmonary syndrome. We describe a case where a female adult diagnosed with congenital extrahepatic portosystemic shunt subsequently developed focal nodular hyperplasia and then hepatocellular carcinoma.

Hepatocellular organellar abnormalities following elimination of hepatitis C virus.

BACKGROUND AND AIMS: The future development of hepatocellular carcinoma (HCC) in patients after sustained virologic response (SVR) is an important issue. The purposes of this study were to investigate pathological alterations in organelle of the liver of SVR patients and to characterize organelle abnormalities that may be related to carcinogenesis after SVR. METHODS: The ultrastructure of liver biopsy specimens from patients with chronic hepatitis C (CHC) and SVR were compared to cell and mouse models and assessed semi-quantitatively using transmission electron microscopy. RESULTS: Hepatocytes in patients with CHC showed abnormalities in the nucleus, mitochondria, endoplasmic reticulum, lipid droplet, and pericellular fibrosis, comparable to those seen in hepatitis C virus (HCV)-infected mice and cells. DAA treatment significantly reduced organelle abnormalities such as the nucleus, mitochondria, and lipid droplet in the hepatocytes of patients and mice after SVR, and cured cells, but it did not change dilated/degranulated endoplasmic reticulum and pericellular fibrosis in patients and mice after SVR. Further, samples from patients with a post-SVR period of >1 year had significantly larger numbers of abnormalities in the mitochondria and endoplasmic reticulum than those of <1 year. A possible cause of organelle abnormalities in patients after SVR could be oxidative stress of the endoplasmic reticulum and mitochondria associated with abnormalities of the vascular system due to fibrosis. Interestingly, abnormal endoplasmic reticulum was associated with patients with HCC for >1 year after SVR. CONCLUSIONS: These results indicate that patients with SVR exhibit a persistent disease state and require long-term follow-up to detect early signs of carcinogenesis.

Gastrointestinal Manifestations Are Associated with Severe COVID-19 in Children.

Purpose: Although less severe than in adults, children can experience a range of COVID-19 symptoms, from asymptomatic to life-threatening, including respiratory and gastrointestinal symptoms. Medical conditions may also increase the severity of the disease in infected children. Methods: This study was performed at a single center, comparing cases and controls, and involving 253 pediatric patients who had been diagnosed with COVID-19. Two different outcomes were assessed. The first categorized symptomatic individuals who were hospitalized with COVID-19 (hospital) from those who were not (nonhospital). The second categorized admitted individuals who spent at least one day in the intensive care unit (ICU) from those who did not require intensive care (floor). Results: Ninety individuals (36%) had at least one underlying medical condition, the most common being pulmonary disorders, such as asthma (12%), followed by neurodevelopmental disorders (8%), gastrointestinal disorders (6%), and seizure disorders (6%). The hospital group was more likely to have a comorbidity, such as obstructive sleep apnea (OSA), diabetes mellitus, seizure disorder, hypertension, sickle cell disease, neurodevelopmental disorder, and immunocompromising conditions, including cancer, bone marrow transplant, and other immunodeficiencies, compared to the non-hospital group. Abdominal pain was more common in the hospital group. Shortness of breath (SOB) and diarrhea were significantly more common in the ICU group than in the floor group. Conclusions: Early identification of pediatric patients with severe COVID-19 is important to improve outcomes. In our single-center case-control study, we found that the presence of gastrointestinal symptoms on presentation was more commonly associated with severe COVID-19 in children.

A multicenter evaluation of hepatitis B reactivation with and without antiviral prophylaxis after kidney transplantation.

BACKGROUND: Hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)-negative and hepatitis B core antibody (anti-HBc)-positive kidney transplant recipients ranges between 1.4% and 9.6%. Limited evidence is available regarding routine antiviral prophylaxis and identifiable risk factors for HBV reactivation in this population. METHODS: In this multicenter retrospective study, we evaluated the prevalence of HBV reactivation in HBsAg-negative anti-HBc-positive kidney transplant recipients who did or did not receive antiviral prophylaxis. The primary outcome assessed the prevalence of HBV reactivation, defined as a positive HBV DNA by PCR of any viral load at or above the minimal detection level. The principal safety outcomes assessed 1-year graft survival, 1-year all-cause mortality, biopsy-proven acute rejection, and antibody-mediated rejection. RESULTS: One hundred and sixty-one patients met inclusion criteria and comprised two groups, antiviral prophylaxis (n = 14) and no antiviral prophylaxis (n = 147). Of patients who did not receive prophylaxis, only five (3.4%) experienced HBV reactivation, whereas one (7.1%) patient in the prophylaxis group experienced reactivation over a median follow-up of 1103 days (p = .43). Furthermore, there were no differences with respect to all secondary outcomes. Statistical analysis demonstrated delayed graft function to be a significant factor associated with HBV reactivation. CONCLUSION: These study results suggest that the prevalence of HBV reactivation in HBsAg-negative anti-HBc-positive kidney transplant recipients is low, regardless of antiviral prophylaxis. Furthermore, there were no significant graft-related outcomes among those that did experience reactivation.

Treatment and outcomes of hepatocellular carcinoma in patients with Sickle cell disease: a population-based study in the U.S.

BACKGROUND: Sickle cell disease (SCD) is a rare hemoglobinopathy which can result in chronic liver disease and cirrhosis. Patients with SCD have an increased risk of hematologic malignancy, but the prevalence of hepatocellular carcinoma (HCC) in this population is unknown. Herein, the association of SCD with HCC was examined using registry data. METHODS: The SEER-Medicare database was queried to identify patients diagnosed with HCC between 2000 and 2015, and further stratified by SCD status. Propensity matching was performed to examine cancer-related survival and treatment outcomes. RESULTS: Overall 56,934 patients with HCC were identified, including 81 patients with SCD. Patients with SCD more frequently had cirrhosis [48.1% (39/81) vs 23.5% (13,377/56,853), p < 0.01] yet presented with smaller tumors [<5 cm: 51.9% (42/81) vs 38.5% (21,898/56,853), p = 0.01]. After propensity matching, SCD was not associated with attenuated survival (aHR 0.73 95%CI 0.52-1.01). When stratified by treatment, patients with SCD had equivalent outcomes to chemotherapy (p = 0.65), TACE/TARE (p = 0.35), resection (p = 0.15) and transplantation (p = 0.67) when compared to non-SCD patients. CONCLUSION: This study confirms that a subset of patients with SCD will develop HCC. Importantly, therapeutic options for HCC should not be limited by pre-existing SCD, and similar survival should be expected when compared to non-SCD patients.

Transfusion-free Retransplantation for Post-liver Transplantation Hepatic Artery Thrombosis: How Much Augmentation Is Too Much?

Liver transplantation presents unique challenges in patients who do not accept blood transfusions. The difficulty of balancing chemical augmentation and handling the technical difficulty of the surgery make transfusion-free liver transplantation an exception rather than the norm. However, at our center, we have performed 27 successful living donor liver transplants in transfusion-free patients. We describe a case of hepatic artery thrombosis (HAT) after living donor liver transplantation requiring retransplantation. This first report of safe retransplantation without blood products demonstrates that even graft-threatening complications can be safely managed in a transfusion-free setting. However, it remains unclear if the medical augmentation to meet hematologic and coagulation parameters before transfusion-free transplantation may increase the risk of postoperative HAT and other thrombotic complications. Although it is our center's experience that the thrombosis rate is comparable with the published rate in standard transfusion-eligible living donor liver transplantations and this case demonstrates that HAT can be safely managed in this setting, further study on the risks and benefits of hematopoietic stimulants as pretransplant optimization is warranted.

Impact of Morbid Obesity on Liver Transplant Candidacy and Outcomes: National and Regional Trends.

BACKGROUND: Body mass index (BMI) limits for liver transplant (LT) candidacy are controversial. In this study, we evaluate waitlist and post-LT outcomes, and prognostic factors and examine regional patterns of LT waitlist registration in patients with BMI ≥40 versus BMI 18-39. METHODS: United Network for Organ Sharing (UNOS) data were analyzed to assess waitlist dropout, post-LT survival, and prognostic factors for patient survival. The distribution of waitlisted patients with BMI ≥40 was compared with the Centers for Disease Control Behavioral Risk Factors Surveillance System data to explore the rates of morbid obesity in the general population of each UNOS region. RESULTS: Post-LT outcomes demonstrate a small but significantly lower 1- and 3-y overall survival for patients with BMI ≥45. Risk factors for post-LT mortality for patients with BMI ≥40 included age >60 y, prior surgery, and diabetes on multivariable analysis. Model for End-Stage Liver Disease >30 was significant on univariable analysis only, likely due to the limited number of patients with BMI ≥40; however, median Model for End-Stage Liver Disease scores in this BMI group were higher than those in patients with lower BMI across all UNOS regions. Patients with BMI ≥40 had a higher waitlist dropout in 4 regions. Comparison with BRFSS data illustrated that the proportion of waitlisted patients with BMI ≥40 was significantly lower than the observed rates of morbid obesity in the general population in 3 regions. CONCLUSIONS: While BMI ≥45 is associated with modestly lower patient survival, careful selection may equalize these numbers.

Diagnosis of Focal Nodular Hyperplasia (FNH) after Liver Transplantation.

Following liver transplantation (LT), recipients can develop benign and malignant hepatic masses just like any other patient. Patients transplanted for hepatocellular carcinoma (HCC) undergo surveillance imaging, and any new mass seen on imaging must be carefully evaluated to rule out recurrent cancer. Focal nodular hyperplasia (FNH) is a benign tumor of the liver that most often occurs in women and is rarely symptomatic. It is important to distinguish FNH from more serious etiologies, such as recurrent HCC and other malignancies, since the treatments differ greatly. To date, there have been very few reports of FNH occurring in a liver allograft. We present a case of a patient with a history of a carcinoid tumor who underwent LT for HCC. Several years posttransplant, the patient was found to have a liver mass with classic features of HCC on imaging. The liver biopsy revealed the unexpected diagnosis of FNH. This finding avoided unnecessary treatment for HCC, which is associated with morbidity, especially in the posttransplant setting. We present our diagnostic approach, discuss the clinicopathologic and imaging findings of FNH, and review the literature on FNH in the posttransplant setting.

The use of organs from hepatitis C virus-viremic donors into uninfected recipients.

PURPOSE OF REVIEW: There has been an ongoing disparity between the number of organs available for solid organ transplantation (SOT) relative to the need. This has resulted in significant waitlist mortality, may affect transplant outcomes due to transplants being performed on sicker patients and may even increase healthcare costs due to extended hospital stays. Transplanting organs from hepatitis C virus (HCV)-infected donors into uninfected recipients (D+/R-) is now a reality, due to the advent of highly affective direct-acting antivirals (DAAs) which not only have very high efficacy, but also a favorable side effect and drug-drug interaction profile. RECENT FINDINGS: Data from multiple centers reporting outcomes of kidney, liver, heart, lung and liver-kidney transplant during the past few years reveal that SOT from HCV-infected donors into noninfected recipients is safe, efficacious and can result in excellent recipient outcomes, with an opportunity to decrease the time on the waitlist, waitlist mortality and to improve outcomes after transplant due to less morbidity at the time of surgery. When livers are the transplanted organ, 8-12 weeks of DAA treatment will be required. For other organs, 2-4 weeks is likely sufficient. The available DAAs have profiles such that patients with all genotypes, with or without renal insufficiency an on renal replacement therapy and those who fail treatment may be successfully treated, with a sustained virologic response rate of more than 95%. Based upon the available data, starting DAAs shortly after transplant will likely limit posttransplant complications. that This will require cooperation between the transplant team, transplant hospital and insurer providing medication coverage. SUMMARY: SOT from HCV infected recipients is safe, is associated with excellent outcomes and should be considered for recipients who would benefit from receiving an organ earlier than they would if they waited for an organ from an uninfected donor.

Fontan-Associated Liver Disease: Screening, Management, and Transplant Considerations.

Surgical innovation and multidisciplinary management have allowed children born with univentricular physiology congenital heart disease to survive into adulthood. An estimated global population of 70 000 patients have undergone the Fontan procedure and are alive today, most of whom are <25 years of age. Several unexpected consequences of the Fontan circulation include Fontan-associated liver disease. Surveillance biopsies have demonstrated that virtually 100% of these patients develop clinically silent fibrosis by adolescence. As they mature, there are increasing reports of combined heart-liver transplantation resulting from advanced liver disease, including bridging fibrosis, cirrhosis, and hepatocellular carcinoma, in this population. In the absence of a transplantation option, these young patients face a poor quality of life and overall survival. Acknowledging that there are no consensus guidelines for diagnosing and monitoring Fontan-associated liver disease or when to consider heart transplantation versus combined heart-liver transplantation in these patients, a multidisciplinary working group reviewed the literature surrounding Fontan-associated liver disease, with a specific focus on considerations for transplantation.

Treatment and Outcomes of Early Stage Breast Cancer in Patients with Hepatic Dysfunction.

BACKGROUND: There exists a dogma of surgical nihilism for patients with cirrhosis and breast cancer causing de-escalation of surgery and impacting survival. We hypothesized that breast cancer surgery would not result in a significant change in the Model for End-Stage Liver Disease-Sodium (MELD-Na) scores before and after surgery. METHODS: We performed a single institutional retrospective review of medical records between January 2013 and July 2019 of patients with concurrent cirrhosis and breast cancer. We used the nonparametric Friedman test to compare differences in MELD-Na scores. RESULTS: Eight patients with both cirrhosis and breast cancer were identified. Median follow-up was 30.5 mo. Half of the patients had Child-Pugh class A cirrhosis and half had Child-Pugh class B cirrhosis. Six (75%) patients underwent lumpectomy and two (25%) underwent mastectomy. There was no statistically significant difference (P = 0.66) in median MELD-Na score before surgery (16) and after surgery (18). Two (25%) patients experienced postoperative complications. Three patients were listed for liver transplantation. Of three listed patients, two (25%) patients underwent successful liver transplantation after breast surgery. One (12.5%) patient died without transplant. Three (37.5%) patients were alive for more than 5 y after breast cancer diagnosis without evidence of cancer recurrence. The eighth patient has remained breast cancer free for more than 6 mo since her surgery. CONCLUSIONS: Surgery for patients with Child-Pugh class A and B cirrhosis and early stage breast cancer did not result in a significant change in MELD-Na score before and after surgery, suggesting that selected patients may benefit from breast cancer surgery with curative intent.

Liver transplantation as therapy for hepatocellular carcinoma.

Liver transplantation can provide curative therapy in selected patients with hepatocellular carcinoma. Well-established criteria include tumours that are within the Milan criteria and without evidence of vascular or extrahepatic involvement. Modest expansion of the original Milan criteria has been shown to achieve similar recurrence-free survival rates. Overall, HCC recurrence occurs in about 10%-15% of LT recipients, most within the first 2 years. Predictors of post-transplant recurrence include high alpha-foetoprotein, macrovascular invasion, as well as tumour size and number. Once HCC recurs after transplantation, prognosis is poor, though better if detected early. There is no established role for systemic prophylactic post-transplant chemotherapy.

Assessment of Fibrosis in Liver Transplant Recipients: Diagnostic Performance of Shear Wave Elastography (SWE) and Correlation of SWE Findings With Biopsy Results.

OBJECTIVE. Liver transplant patients are monitored for rejection and hepatic fibrosis and often undergo liver biopsies. The purpose of the present study is to determine whether noninvasive shear wave elastography (SWE) can quantify fibrosis in liver transplant recipients, with the aim of decreasing and possibly eliminating unnecessary biopsies for patients with suspected or progressive hepatic fibrosis. MATERIALS AND METHODS. Between May 1, 2015, and December 31, 2017, our prospective study evaluated 111 adult liver transplant patients (age range, 23-79 years) who underwent 147 ultrasound (US) SWE examinations of the right hepatic lobe followed by biopsies. SWE values were compared with the histologic fibrosis (Metavir) scores of the biopsy samples. SWE threshold values were determined using classification and regression tree analysis by anchoring to the degree of fibrosis. The sensitivity, specificity, positive predictive value, and negative predictive value (with 95% CIs) were calculated on the basis of the threshold value. Overall prediction accuracy was estimated using the AUC value from the ROC curve. RESULTS. From the 147 US SWE examinations and liver biopsies, consistent threshold values were identified for patients with no or minimal fibrosis (Metavir scores of F0 and F1, respectively) compared with significant fibrosis (Metavir scores of F2, F3, or F4). A median SWE value of 1.76 m/s or less denoted no or minimal fibrosis, whereas a value greater than 1.76 m/s denoted significant fibrosis. The sensitivity of US SWE examinations in classifying fibrosis was 0.77 (95% CI, 0.5-0.93). The specificity, positive predictive value, and negative predictive value were 0.79 (95% CI, 0.71-0.86), 0.33 (95% CI, 0.19-0.49), and 0.96 (95% CI, 0.91-0.99), respectively. CONCLUSION. Liver transplant patients may avoid liver biopsy if US SWE examination shows a median shear wave velocity of 1.76 or less, which corresponds to a Metavir score of F0 or F1, denoting no or minimal fibrosis.

Evolving ethics, policy and reimbursement issues of vascularized composite allotransplantation: Symposium summary.

In this article, we present a report from a national meeting titled, "Evolving Issues of Vascularized Composite Allotransplantation-A Symposium on Ethics, Policy, and Reimbursement Issues," which convened in September 2017. We discuss the maturation of vascularized composite allotransplantation from an emerging technology to becoming an extension of clinical practice for select patients with complex reconstructive needs. Viewpoints and action items were presented by and discussed among the 70+ clinicians, researchers, policymakers, ethicists, healthcare administrators, and third-party payers who attended the symposium with the goals of implementing a collaborative roadmap for vascularized composite allotransplantation growth, evaluation, and sustainability by establishing a unified plan to help address concerns of the public, policymakers, and healthcare finance. We review the current status of vascularized composite allotransplantation in clinical practice and summarize symposium discussions regarding ethical considerations, reimbursement, payer strategies, and standardization of data collection.

Comparison of Skin Cancer Incidence in Caucasian and Non-Caucasian Liver Vs. Lung Transplant Recipients: A Tale of Two Regimens.

BACKGROUND: Organ transplantation is a significant risk factor for the development of skin cancer. The impact of skin type, immunosuppressive regimens, and photosensitizing agents requires further study. OBJECTIVE: The objective of this study was to compare skin cancer development between Caucasian and non-Caucasian transplant recipients at the University of Southern California. METHODS: We performed a retrospective chart review of lung and liver transplantations to determine the incidence of post-transplant skin cancer. Participants included patients who underwent lung or liver transplantation between 2005 and 2013 at our institution. Patients included in the study were limited to those who survived through the study observation period. RESULTS: We analyzed 475 patients who underwent transplantation, including 370 liver transplant recipients and 105 lung transplant recipients. Among these, 46.3% identified as Caucasian, while 53.7% were non-Caucasian. Over a mean follow-up of 7.9 years, 11.8% of Caucasian patients developed at least one skin cancer, compared with 2.7% of non-Caucasians (p < 0.001). However, irrespective of race, skin cancer development was significantly greater in lung compared with liver transplant recipients (20.0% vs. 3.2%, p < 0.001). The standard immunosuppressive and prophylactic regimens were mycophenolate mofetil and tacrolimus based for both transplants. Mycophenolate mofetil was maintained throughout the course in lung transplant patients, whereas this agent was reduced and terminated when possible in liver transplant recipients. In addition, during the years examined, voriconazole, a known photosensitizing agent, was used in lung transplant recipients to prevent aspergillosis. CONCLUSIONS: Fair skin type increases post-transplant skin cancer development, irrespective of the immunosuppressive regimen. A higher risk of skin cancer is associated with different regimens; in particular photosensitizing agents may increase risk in transplant recipients.

Early trauma, attachment experiences and comorbidities in schizophrenia / Relação entre traumas precoces, experiências de apego e comorbidades na esquizofrenia

Abstract Objective To evaluate attachment patterns in subjects with schizophrenia and their relationships to early traumatic events, psychotic symptoms and comorbidities. Methods Twenty patients diagnosed with schizophrenia according to criteria from the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) underwent retrospective symptom assessment and careful assessment of the number and manner of childhood caregiver changes. The Diagnostic Interview for Psychosis and Affective Disorders (DI-PAD) was used to assess symptoms related to schizophrenia (positive and negative symptoms), depression and mania. Anxiety disorder comorbidities were assessed by the Liebowitz Social Anxiety Scale (LSAS), Yale-Brown Obsessions and Compulsions Scale (Y-BOCS) and Panic and Schizophrenia Interview (PaSI). Experience in Close Relationships - Relationship Structures (ECR-RS) and Early Trauma Inventory Self Report-Short Form (ETISR-SF) were used to assess attachment patterns and traumatic history, respectively. Results Moderate and significant correlations between attachment patterns and early trauma showed that greater severity of anxious attachment was predicted by a higher frequency of total early traumas (Spearman ρ = 0.446, p = 0.04), mainly general traumas (ρ = 0.526, p = 0.017; including parental illness and separation, as well as natural disaster and serious accidents). Among the correlations between early trauma and comorbid symptoms, panic attacks occurring before the onset of schizophrenia showed significant and positive correlations with ETISR-SF total scores and the sexual trauma subscale. Conclusion Children with an unstable early emotional life are more vulnerable to the development of psychopathology, such as panic anxiety symptoms. Traumatic events may also predict later schizophrenia.

Resumo Objetivos Avaliar o padrão de apego em portadores de esquizofrenia e discutir a relação que tais padrões apresentam com a sintomatologia psicótica e as comorbidades dos pacientes investigados. Métodos Vinte pacientes diagnosticados com esquizofrenia de acordo com os critérios do Manual Diagnóstico e Estatístico de Transtornos Mentais, 5ª edição (DSM-5) foram submetidos a avaliação de sintomas retrospectivos e avaliação cuidadosa do número e modo de mudança de cuidador da infância. A Entrevista Diagnóstica para Psicoses e Transtornos Afetivos (DI-PAD) foi utilizada para avaliar sintomas relacionados à esquizofrenia (sintomas positivos e negativos), depressão e mania. As comorbidades de transtorno de ansiedade foram avaliadas pela Escala de Ansiedade Social de Liebowitz (LSAS), Escala de Sintomas Obsessivo-Compulsivos de Yale-Brown (Y-BOCS) e Entrevista de Pânico e Esquizofrenia (PaSI). Os instrumentos Questionário das Experiências nas Relações Próximas-Estruturas Relacionais (ECR-RS) e Inventário de Autorrelato de Trauma Precoce - Forma Curta (ETISR-SF) foram utilizados para avaliar padrões de apego e histórico traumático, respectivamente. Resultados Foram identificadas correlações significativas entre a ocorrência de traumas precoces e o apego do tipo ansioso. Também foi verificada a relação entre traumas gerais e sintomas de pânico, constatando-se que as crises de pânico antecipam surtos quando predominam sintomas ansiosos, somáticos, alucinações e ideias delirantes. Foi observado que a ocorrência de traumas precoces contribui para o pânico, elevando o risco de episódios psicóticos. Conclusão . Os resultados indicam que as adversidades ambientais na infância estão associadas com o risco de desenvolvimento de esquizofrenia e de outras psicoses mais tarde na vida.

Distinct patterns of innate immune activation by clinical isolates of respiratory syncytial virus.

Respiratory syncytial virus (RSV) is a major respiratory pathogen of infants and young children. Multiple strains of both subgroup A and B viruses circulate during each seasonal epidemic. Genetic heterogeneity among RSV genomes, in large part due to the error prone RNA-dependent, RNA polymerase, could mediate variations in pathogenicity. We evaluated clinical strains of RSV for their ability to induce the innate immune response. Subgroup B viruses were used to infect human pulmonary epithelial cells (A549) and primary monocyte-derived human macrophages (MDM) from a variety of donors. Secretions of IL-6 and CCL5 (RANTES) from infected cells were measured following infection. Host and viral transcriptome expression were assessed using RNA-SEQ technology and the genomic sequences of several clinical isolates were determined. There were dramatic differences in the induction of IL-6 and CCL5 in both A549 cells and MDM infected with a variety of clinical isolates of RSV. Transcriptome analyses revealed that the pattern of innate immune activation in MDM was virus-specific and host-specific. Specifically, viruses that induced high levels of secreted IL-6 and CCL5 tended to induce cellular innate immune pathways whereas viruses that induced relatively low level of IL-6 or CCL5 did not induce or suppressed innate immune gene expression. Activation of the host innate immune response mapped to variations in the RSV G gene and the M2-1 gene. Viral transcriptome data indicated that there was a gradient of transcription across the RSV genome though in some strains, RSV G was the expressed in the highest amounts at late times post-infection. Clinical strains of RSV differ in cytokine/chemokine induction and in induction and suppression of host genes expression suggesting that these viruses may have inherent differences in virulence potential. Identification of the genetic elements responsible for these differences may lead to novel approaches to antiviral agents and vaccines.