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.

Comparison of early risk factors between healthy siblings and subjects with schizophrenia and bipolar disorder.

Introduction: The following work aims to compare the types and magnitude of risk events in patients with Schizophrenia and Bipolar Disorder and each of those groups with of a group of healthy siblings, exploring differences and similarities of the two psychotic disorders. Methods: Retrospective interviews were conducted with 20 families to investigate maternal and obstetric health, social support and the presence of early trauma for the affected family members and healthy siblings. Mothers were interviewed with the Prenatal Psychosocial Profile and each family participant was assessed with the Early Trauma Inventory, Screening Questionnaire of the Genomic Psychiatry Cohort and the Diagnostic Interview for Psychosis and Affective Disorders. Results: Obstetric and gestational history, pregnancy weight changes and early trauma were associated with offspring's mental illness, including statistically significant findings for complications of pregnancy, pregnancy weight changes, general trauma, physical punishment and emotional abuse. Conclusion: These findings highlight the different risk factor exposures that occur within a family, which may increase the risk for severe mental illness.

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.

The ethics of using COVID-19 host genomic information for clinical and public health decision-making: A survey of US health professionals.

Several genetic variants linked to COVID-19 have been identified by host genomics researchers. Further advances in this research will likely play a role in the clinical management and public health control of future infectious disease outbreaks. The implementation of genetic testing to identify host genomic risk factors associated with infectious diseases raises several ethical, legal, and social implications (ELSIs). As an important stakeholder group, health professionals can provide key insights into these ELSI issues. In 2021, a cross-sectional online survey was fielded to US health professionals. The survey explored how they view the value and ethical acceptability of using COVID-19 host genomic information in three main decision-making settings: (1) clinical, (2) public health, and (3) workforce. The survey also assessed participants' personal and professional experience with genomics and infectious diseases and collected key demographic data. A total of 603 participants completed the survey. A majority (84%) of participants agreed that it is ethically acceptable to use host genomics to make decisions about clinical care and 73% agreed that genetic screening has an important role to play in the public health control of COVID-19. However, more than 90% disagreed that it is ethically acceptable to use host genomics to deny resources or admission to individuals when hospital resources are scarce. Understanding stakeholder perspectives and anticipating ELSI issues will help inform policies for hospitals and public health departments to evaluate and perhaps adopt host genomic technologies in an ethically and socially responsible manner during future infectious disease outbreaks.

Cognition in Schizophrenia: A Systematic Review of Wechsler Adult Intelligence Scale Studies.

Objective: To critically analyze the evidence regarding changes in verbal and performance intelligence quotient (IQ) in patients with schizophrenia.Data Sources: An English-language-only search was conducted in the PubMed, Cochrane Library, and LILACS databases for articles with study objectives that included Wechsler Adult Intelligence Scale (WAIS) assessment of cognitive functions in patients with schizophrenia. Descriptors were defined based on Medical Subject Headings, where associations of psychotic disorders related to the schizophrenia spectrum were suggested, as well as the "Wechsler Scales" descriptor. The search was conducted in November 2022 with no restriction on the date of publication to select studies that used any of the WAIS editions.Study Selection: Articles that met the inclusion criteria were selected after title and summary identification and full-text review.Results: A total of 28 articles were identified. All studies presented total IQ scores, but only 20 showed results for verbal IQ (n = 20) or performance IQ (n = 19). Analyzed data indicated patients had average performance on verbal comprehension features but low average performance on perceptual reasoning, working memory, and processing speed indices.Conclusions: Executive function deficits were found in the analyzed studies, which reflect difficulties in planning and impulse control-characteristics present in the diagnosis of schizophrenia. The identification of this neuropsychological functioning contributes to the understanding of the cognitive dynamics found in schizophrenia and may help in early diagnosis, reinforcing the hypothesis that cognitive performance may be one of the indicators of psychopathologic expression.Prim Care Companion CNS Disord 2023;25(5):22r03456. Author affiliations are listed at the end of this article.

Persistent symptoms and conditions among children and adolescents hospitalised with COVID-19 illness: a qualitative study.

OBJECTIVES: There is limited in-depth research exploring persistent symptoms and conditions among children and adolescents who contracted COVID-19 illness that required hospitalisation. The main objective of this study was to conduct qualitative interviews among families who had a child hospitalised with COVID-19 illness to elucidate their child's physical, mental and social health outcomes months after initial acute infection. DESIGN, SETTING AND PARTICIPANTS: A qualitative study that composed of in-depth interviews among families with a child hospitalised with COVID-19 illness in one large urban US paediatric healthcare system. Parents (N=25) were recruited from an ongoing quantitative study to estimate the prevalence of long COVID in children hospitalised with COVID-19 illness. During in-depth interviews, parents were invited to describe their child's post-COVID-19 symptoms and experiences. Interviews were audiotaped, transcribed and coded in NVivo. RESULTS: Seven themes were identified concerning the child's prolonged COVID-19 experiences: (1) post-traumatic stress disorder, (2) social anxiety, (3) severe symptoms on reinfection, (4) worsened pre-existing conditions, (5) lack of insurance coverage for costly treatments, (6) access and utilisation of support systems and (7) overall resilience and recovery. Four parent-specific themes were identified: (1) fear of COVID-19 unknowns, (2) mixed messaging from health information sources, (3) schools being both a support system and a hindrance and (4) desire for and access to support systems. CONCLUSIONS: A subset of children who were hospitalised with COVID-19 illness are experiencing a range of serious mental health impacts related to persistent COVID-19 symptoms. Clinical and public health support strategies should be developed to support these children and their families as they reintegrate in school, social and community activities.

Clinical Significance of Ascitic Fluid Polymorphonuclear Leukocyte Percentage in Patients With Cirrhosis Without Spontaneous Bacterial Peritonitis.

INTRODUCTION: Absolute polymorphonuclear leukocyte (PMN) count (PMN-C) ≥250 cells/mm 3 in ascites is the diagnostic hallmark of spontaneous bacterial peritonitis (SBP) and is associated with high morbidity and mortality. However, the clinical significance of ascitic PMN percentage (PMN-%) and PMN-C in the absence of SBP as additional biomarkers for mortality and future incidence of SBP has not been determined. METHODS: This retrospective cohort included adults with cirrhosis undergoing first-recorded paracentesis with initial PMN-C < 250 cells/mm 3 at 2 tertiary medical centers between 2015 and 2020. Patients with prior SBP were excluded. Outcomes were death and SBP development. Cox regression estimated hazard ratios (HRs) for risk of death and SBP development and Akaike information criterion to compare model fit. RESULTS: Three hundred eighty-four adults (73% male, median age 58 years, 67% with alcohol-associated cirrhosis, median PMN-C 14 cells/mm 3 [interquartile range 5-34], and median PMN-% 10% [interquartile range 4-20]) were included in this study. Univariate risk of death increased 10% per 25-unit increase in PMN-C (95% confidence interval 1.01-1.21, P = 0.03) and 19% per 10-unit increase in PMN-% (95% confidence interval 1.06-1.33, P = 0.003) with PMN-% demonstrating better model fit in assessing mortality risk (Akaike information criterion: 1,044 vs 1,048, respectively). In models adjusted for age, chronic hepatitis C virus infection, and Model for End-Stage Liver Disease-Sodium, PMN-% was associated with risk of death (PMN-% 10%-29%, HR 1.17, P = 0.50; PMN-% ≥ 30% group, HR 1.94, P = 0.03; vs PMN-% < 10%) and SBP development (PMN-% 10%-29%, HR 1.68, P = 0.07; PMN-% ≥ 30%, HR 3.48, P < 0.001; vs PMN-% < 10%). DISCUSSION: Our results suggest PMN-% at first paracentesis represents a better biomarker compared with PMN-C for assessing risk of death and future SBP development in patients with PMN-C < 250 cells/mm 3 .

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.

Impact of Bacteria Types on the Clinical Outcomes of Spontaneous Bacterial Peritonitis.

BACKGROUND AND AIMS: Cirrhotic patients presenting with spontaneous bacterial peritonitis (SBP) have elevated risk of short-term mortality. While high Model for End-Stage Liver Disease-Sodium score (MELD-Na) and ascites culture yielding multi-drug resistance (MDR) bacteria are well established risk factors for further aggravating mortality, the impact of individual, causative microorganisms and their respective pathogenesis have not been previously investigated. METHODS: This is a retrospective study of 267 cirrhotic patients at two tertiary care hospitals undergoing paracentesis from January 2015 to January 2021 who presented with ascitic PMN count > 250 cells/mm3. The primary outcome was SBP progression defined as death or liver transplantation within 1-month of paracentesis stratified by microorganism type. RESULTS: Of 267 patients with SBP, the ascitic culture yielded causative microorganism in 88 cases [median age 57 years (IQR 52-64)]; 68% male; median MELD-Na 29 (IQR 23-35). The microbes isolated were E. coli (33%), Streptococcus (15%), Klebsiella (13%), Enterococcus (13%), Staphylococcus (9%) and others (18%); 41% were MDR. Cumulative incidence of SBP progression within 1-month was 91% (95% CI 67-100) for Klebsiella, 59% (95% CI 42-76) for E. coli, and 16% (95% CI 4-51) for Streptococcus. After adjusting for MELD-Na and MDR, risk of SBP progression remained elevated for Klebsiella (HR 2.07; 95% CI 0.98-4.24; p-value = 0.06) and decreased for Streptococcus (HR 0.28; 95% CI 0.06-1.21; p-value = 0.09) compared to all other bacteria. CONCLUSION: Our study found Klebsiella-associated SBP had worse clinical outcomes while Streptococcus-associated SBP had the most favorable outcomes after accounting for MDR and MELD-Na. Thus, identification of the causative microorganism is crucial not only for optimizing the treatment but for prognostication.

Feeling pressured to talk about trauma: How pressure to disclose alters the association between trauma disclosure and posttraumatic growth.

Talking with others about traumatic experiences (i.e., trauma disclosure) has been associated with increased posttraumatic growth (PTG). Although this association indicates the value of disclosing, there is evidence that external pressure to disclose can hinder the benefits of trauma disclosure. The aim of the current study was to examine the influence of pressure to disclose on the association between trauma disclosure and PTG. People who had experienced a traumatic event and disclosed their trauma to a close other were recruited using Amazon's Mechanical Turk (N = 208). Participants completed measures of trauma exposure, trauma disclosure, pressure to disclose, PTG, posttraumatic stress symptoms, and response to disclosure. The results indicated that the linear association between trauma disclosure and PTG was quadratically moderated by pressure to disclose, ηp 2 = .025. Pressure to disclose strengthened the positive association between trauma disclosure and PTG from low, B = 0.818 (SE = 0.267), to moderate levels of pressure, B = 2.109 (SE = 0.471). However, when pressure was high, the association between disclosure and PTG was not significant, B = -1.19 (SE = 1.327). These findings indicate that a moderate amount of pressure to disclose may facilitate the positive impact of disclosure on PTG, yet a high amount of pressure may impede the positive association between disclosure and PTG. This research furthers understanding of the nuances of trauma disclosure and how close others' involvement in disclosure can impact the process of PTG for trauma survivors.

First Organoid Intelligence (OI) workshop to form an OI community.

The brain is arguably the most powerful computation system known. It is extremely efficient in processing large amounts of information and can discern signals from noise, adapt, and filter faulty information all while running on only 20 watts of power. The human brain's processing efficiency, progressive learning, and plasticity are unmatched by any computer system. Recent advances in stem cell technology have elevated the field of cell culture to higher levels of complexity, such as the development of three-dimensional (3D) brain organoids that recapitulate human brain functionality better than traditional monolayer cell systems. Organoid Intelligence (OI) aims to harness the innate biological capabilities of brain organoids for biocomputing and synthetic intelligence by interfacing them with computer technology. With the latest strides in stem cell technology, bioengineering, and machine learning, we can explore the ability of brain organoids to compute, and store given information (input), execute a task (output), and study how this affects the structural and functional connections in the organoids themselves. Furthermore, understanding how learning generates and changes patterns of connectivity in organoids can shed light on the early stages of cognition in the human brain. Investigating and understanding these concepts is an enormous, multidisciplinary endeavor that necessitates the engagement of both the scientific community and the public. Thus, on Feb 22-24 of 2022, the Johns Hopkins University held the first Organoid Intelligence Workshop to form an OI Community and to lay out the groundwork for the establishment of OI as a new scientific discipline. The potential of OI to revolutionize computing, neurological research, and drug development was discussed, along with a vision and roadmap for its development over the coming decade.

Living donor liver paired exchange between pediatric and adult recipients due to donor graft size mismatch.

Living donor liver transplantation is an effective means to decrease organ shortage. However, many potential living donors are currently being denied due to ABO incompatibility or inadequate donor liver volume. Liver paired exchange (LPE) provides a practical solution to overcome these obstacles, and yet the first case of LPE in the United States was only recently reported in 2020. Here, we report world's first case of LPE involving pediatric and adult recipients to avoid surgical complexity of the pediatric recipient and to increase the graft-to-recipient weight ratio of the adult recipient between 2 ABO compatible pairs. As living donor liver transplantation becomes more widely adopted, the need for pair exchange to improve surgical safety and postoperative outcomes between 2 ABO compatible pairs is likely to increase.

Addressing sex-based disparities in liver transplantation.

PURPOSE OF REVIEW: Disparities in access to liver transplantation by sex have been well described, disadvantaging women. Understanding the multifactorial causes of these disparities as well as the variety of proposed solutions is critical to improving access to this life-saving intervention for women. This review aims to summarize the current body of evidence on observed sex disparities in liver transplantation and highlight actionable, evidence-based mechanisms by which these disparities can be addressed. RECENT FINDINGS: Strategies for addressing sex disparities in liver transplantation include increasing organ utilization, changing allocation policy, and leveraging public policies to reduce the incidence of end-stage liver disease. Several other promising interventions are currently being explored. SUMMARY: In the United States, women face additional barriers to liver transplantation on the basis of sex. Immediate action is necessary to systematically address these inequities.

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.

Gold Nanourchins Improve Virus Targeting and Plasmonic Coupling for Virus Diagnosis on a Smartphone Platform.

Point-of-care detection of pathogens is critical to monitor and combat viral infections. The plasmonic coupling assay (PCA) is a homogeneous assay and allows rapid, one-step, and colorimetric detection of intact viruses. However, PCA lacks sufficient sensitivity, necessitating further mechanistic studies to improve the detection performance of PCA. Here, we demonstrate that gold nanourchins (AuNUs) provide significantly improved colorimetric detection of viruses in PCA. Using respiratory syncytial virus (RSV) as a target, we demonstrate that the AuNU-based PCA achieves a detection limit of 1400 PFU/mL, or 17 genome equivalent copies/µL. Mechanistic studies suggest that the improved detection sensitivity arises from the higher virus-binding capability and stronger plasmonic coupling at long distances (∼10 nm) by AuNU probes. Furthermore, we demonstrate the virus detection with a portable smartphone-based spectrometer using RSV-spiked nasal swab clinical samples. Our study uncovers important mechanisms for the sensitive detection of intact viruses in PCA and provides a potential toolkit at the point of care.

Why the World Needs Bioethics Communication.

This essay argues for the importance of formalizing public engagement efforts around bioethics as something we might call "bioethics communication," and it outlines the Johns Hopkins Berman Institute of Bioethics' plans for engaging in this effort. Because science is complex and difficult to explain to nonexperts, the field of science communication has arisen to meet this need. The field involves both a practice and a subject of empirical research. Like science, bioethics is also complex and difficult to explain, which is why the world needs bioethics communication. The authors are engaged in a brand-new effort to establish the sort of public bioethics efforts that would constitute bioethics communication, through a program which they call the Dracopoulos-Bloomberg iDeas Lab. The authors invite colleagues to experiment and learn with them as they invest in the development of bioethics communicators and their products.