Isolated Atrial Neutrophilic Myocarditis: A Rare Cause of Death and Potential "Blind Spot" for Postmortem Computed Tomography and Postmortem Examination.

ABSTRACT: Myocarditis can focally or diffusely involve the myocardium and is associated with arrhythmia, cardiac failure, and sudden death. The majority of cases of myocarditis are lymphocytic in etiology, and neutrophilic myocarditis is relatively uncommon. Although reported in lymphocytic myocarditis, isolated/focal neutrophilic myocarditis of the atrium causing death is not reported in the postmortem literature, and its postmortem computed tomography correlation is not documented. We report a fatal case of isolated neutrophilic atrial myocarditis affecting only the left atrium in a 33-year-old woman presenting as a sudden unexpected death. Microscopy of the left atrium, a not commonly sampled area of the heart, showed florid neutrophilic myocarditis with the remaining right atrium, conduction system, and both ventricles uninvolved. Similar to previously reported fatal isolated atrial lymphocytic myocarditis, postmortem computed tomography was unable to detect any atrial abnormalities. This case highlights a potential "blind spot" for both routine postmortem imaging and examination.

Cervical Epidural Abscess: A Blind Spot for Postmortem Computed Tomography.

ABSTRACT: Spinal epidural abscess is an uncommon condition, which may have serious complications, including neurological sequelae and death. Classical symptoms include spinal pain, fever, and neurological deficit; however, diagnosis is difficult and requires a high degree of clinical suspicion. Antemortem magnetic resonance imaging (MRI) scanning is the gold-standard diagnostic tool. Computed tomography (CT) is less sensitive and as such, postmortem CT may miss the diagnosis. We report a case of Staphylococcus aureus cervical epidural abscess presenting as neck pain and causing flaccid paralysis and subsequently death. Antemortem MRI showed a small epidural collection, spinal cord edema, and fluid in the adjacent cervical disc and facet joints; however, these findings could not be appreciated on postmortem CT. Postmortem examination, guided by the antemortem imaging, was able to confirm a cervical spinal epidural abscess; however, similar deaths may occur before medical presentation. This case demonstrates a limitation of postmortem imaging in diagnosing spinal epidural abscess and highlights that such cases may be missed.

Phlegmonous Psoas Muscle Infection Causing Sepsis and Death With Missing Postmortem Computed Tomography Scan Correlation.

ABSTRACT: Infection of the psoas muscle is a rare pathology, which carries a high risk of sepsis and is a potential cause of death. Classic symptoms include back pain and fever and it may be diagnosed premortem on computed tomography or magnetic resonance imaging, where abscess formation may be identified as a discrete rim enhancing and low-attenuation lesion. Infections without abscess formation, such as phlegmonous infection, may be more difficult to identify however, particularly if there is absence of other nonspecific findings, such as gas bubbles. We report a case of Staphylococcus aureus phlegmonous psoas muscle causing sepsis and death with no postmortem computed tomography scan correlation, where clinical history of back pain and an unknown source of sepsis was the only prompt for psoas dissection. This case highlights a potential postmortem computed tomography blind spot in abdominal pathology and we recommend dissecting the psoas muscle if sepsis is suspected but a definitive septic focus is unable to be identified.

Titanium Fan Plate Reconstruction for Lateral Orbital Traumatic Defects.

ABSTRACT: Fractures of the orbit often require operative repair with materials ranging from autologous tissue to titanium implants. Reconstructive techniques of the lateral orbital rim and wall offer a unique challenge due to the structural and aesthetic demands with regard to its natural contour. The authors present a case in which a patient sustained a ballistic injury involving the lateral orbital rim and wall requiring reconstruction. The authors employed the use of a single titanium orbital mesh fan plate (DePuy Synthes, Warsaw IN) in an injury-specific and cost-effective technique to rapidly restore the contour and structure of the lateral orbit rivaling the result of a 3D printed custom plate.

Disproportionate Sterilization of Latinos Under California's Eugenic Sterilization Program, 1920-1945.

OBJECTIVES: To compare population-based sterilization rates between Latinas/os and non-Latinas/os sterilized under California's eugenics law. METHODS: We used data from 17 362 forms recommending institutionalized patients for sterilization between 1920 and 1945. We abstracted patient gender, age, and institution of residence into a data set. We extracted data on institution populations from US Census microdata from 1920, 1930, and 1940 and interpolated between census years. We used Spanish surnames to identify Latinas/os in the absence of data on race/ethnicity. We used Poisson regression with a random effect for each patient's institution of residence to estimate incidence rate ratios (IRRs) and compare sterilization rates between Latinas/os and non-Latinas/os, stratifying on gender and adjusting for differences in age and year of sterilization. RESULTS: Latino men were more likely to be sterilized than were non-Latino men (IRR = 1.23; 95% confidence interval [CI] = 1.15, 1.31), and Latina women experienced an even more disproportionate risk of sterilization relative to non-Latinas (IRR = 1.59; 95% CI = 1.48, 1.70). CONCLUSIONS: Eugenic sterilization laws were disproportionately applied to Latina/o patients, particularly Latina women and girls. Understanding historical injustices in public health can inform contemporary public health practice.

The National Kidney Foundation of Illinois KidneyMobile: a mobile resource for community based screenings of chronic kidney disease and its risk factors.

BACKGROUND: Early detection and treatment of chronic kidney disease (CKD) and its risk factors improves outcomes; however, many high-risk individuals lack access to healthcare. The National Kidney Foundation of Illinois (NKFI) developed the KidneyMobile (KM) to conduct community-based screenings, provide disease education, and facilitate follow-up appointments for diabetes, hypertension, and CKD. METHODS: Cross-sectional design. Adults > = 18 years of age participated in NKFI KM screenings across Illinois between 2005 and 2011. Sociodemographic and medical history were self-reported using structured interviews; laboratory data and blood pressure were assessed using standard procedures. RESULTS: Among 20,770 participants, mean age was 53.5 years, 68% were female, 49% were African-American or Hispanic, 21% primarily spoke Spanish, and at least 27% lacked health insurance. Seventy-eight percent of participants with elevated blood pressure (≥ 140/90 mmHg) were aware of having hypertension, 93% of participants with abnormal blood glucose (fasting glucose > 126 mg/dl or a random glucose of > 200 mg/dL) were aware of having diabetes, and 19% of participants with albuminuria (> 30 mg/gm) were aware of having CKD. In participants reporting hypertension, 47% had blood pressure ≥ 140/90 mmHg, and in those reporting diabetes, 56% had blood glucose ≥ 130 mg/dl (fasting) or ≥ 180 mg/dl (random). Among 4937 participants with abnormal screening findings that participated in follow-up interviews, 69% reported having further medical evaluation. CONCLUSIONS: A high-risk disadvantaged population is being reached by the NKFI KidneyMobile and connected with healthcare services. A significant proportion of participants were newly informed of having abnormal results suggestive of diabetes, hypertension, and/or CKD or that their diabetes and hypertension were inadequately controlled.

A novel immune biomarker IFI27 discriminates between influenza and bacteria in patients with suspected respiratory infection.

Host response biomarkers can accurately distinguish between influenza and bacterial infection. However, published biomarkers require the measurement of many genes, thereby making it difficult to implement them in clinical practice. This study aims to identify a single-gene biomarker with a high diagnostic accuracy equivalent to multi-gene biomarkers.In this study, we combined an integrated genomic analysis of 1071 individuals with in vitro experiments using well-established infection models.We identified a single-gene biomarker, IFI27, which had a high prediction accuracy (91%) equivalent to that obtained by multi-gene biomarkers. In vitro studies showed that IFI27 was upregulated by TLR7 in plasmacytoid dendritic cells, antigen-presenting cells that responded to influenza virus rather than bacteria. In vivo studies confirmed that IFI27 was expressed in influenza patients but not in bacterial infection, as demonstrated in multiple patient cohorts (n=521). In a large prospective study (n=439) of patients presented with undifferentiated respiratory illness (aetiologies included viral, bacterial and non-infectious conditions), IFI27 displayed 88% diagnostic accuracy (AUC) and 90% specificity in discriminating between influenza and bacterial infections.IFI27 represents a significant step forward in overcoming a translational barrier in applying genomic assay in clinical setting; its implementation may improve the diagnosis and management of respiratory infection.

California's Sterilization Survivors: An Estimate and Call for Redress.

From 1919 to 1952, approximately 20 000 individuals were sterilized in California's state institutions on the basis of eugenic laws that sought to control the reproductive capacity of people labeled unfit and defective. Using data from more than 19 000 sterilization recommendations processed by state institutions over this 33-year period, we provide the most accurate estimate of living sterilization survivors. As of 2016, we estimate that as many as 831 individuals, with an average age of 87.9 years, are alive. We suggest that California emulate North Carolina and Virginia, states that maintained similar sterilization programs and recently have approved monetary compensation for victims. We discuss the societal obligation for redress of this historical injustice and recommend that California seriously consider reparations and full accountability.

The CYP27B1 variant associated with an increased risk of autoimmune disease is underexpressed in tolerizing dendritic cells.

Genome-wide association studies have identified a linkage disequilibrium (LD) block on chromosome 12 associated with multiple sclerosis (MS), type 1 diabetes and other autoimmune diseases. This block contains CYP27B1, which catalyzes the conversion of 25 vitamin D3 (VitD3) to 1,25VitD3. Fine-mapping analysis has failed to identify which of the 17 genes in this block is most associated with MS. We have previously used a functional approach to identify the causal gene. We showed that the expression of several genes in this block in whole blood is highly associated with the MS risk allele, but not CYP27B1. Here, we show that CYP27B1 is predominantly expressed in dendritic cells (DCs). Its expression in these cells is necessary for their response to VitD, which is known to upregulate pathways involved in generating a tolerogenic DC phenotype. Here, we utilize a differentiation protocol to generate inflammatory (DC1) and tolerogenic (DC2) DCs, and show that for the MS risk allele CYP27B1 is underexpressed in DCs, especially DC2s. Of the other Chr12 LD block genes expressed in these cells, only METT21B expression was as affected by the genotype. Another gene associated with autoimmune diseases, CYP24A1, catabolizes 1,25 VitD3, and is predominantly expressed in DCs, but equally between DC1s and DC2s. Overall, these data are consistent with the hypothesis that reduced VitD pathway gene upregulation in DC2s of carriers of the risk haplotype of CYP27B1 contributes to autoimmune diseases. These data support therapeutic approaches aimed at targeting VitD effects on DCs.

Modeling problem behaviors in a nationally representative sample of adolescents.

Research on multiple problem behaviors has focused on the concept of Problem Behavior Syndrome (PBS). Problem Behavior Theory (PBT) is a complex and comprehensive social-psychological framework designed to explain the development of a range of problem behaviors. This study examines the structure of PBS and the applicability of PBT in adolescents. Participants were 6062 adolescents; aged 12-19 (51.3% female) who took part in the My World Survey-Second Level (MWS-SL). Regarding PBS, Confirmatory Factor Analysis established that problem behaviors, such as alcohol and drug use loaded significantly onto a single, latent construct for males and females. Using Structural Equation Modeling, the PBT framework was found to be a good fit for males and females. Socio-demographic, perceived environment system and personality accounted for over 40% of the variance in problem behaviors for males and females. Our findings have important implications for understanding how differences in engaging in problem behaviors vary by gender.

A Website Intervention to Increase Knowledge About Living Kidney Donation and Transplantation Among Hispanic/Latino Dialysis Patients.

BACKGROUND: Hispanic dialysis patients often encounter barriers to learning about living kidney donation and transplantation. Effective culturally targeted interventions to increase knowledge are lacking. We developed a culturally targeted educational website to enhance informed treatment decision making for end-stage kidney disease. METHODS: A pretest/posttest intervention study was conducted among adult Hispanic patients undergoing dialysis at 5 dialysis centers in Chicago, Illinois. Surveys included a 31-item, multiple-choice pretest/posttest of knowledge about kidney transplantation and living donation, attitudes about the website, Internet use, and demographics. The intervention entailed viewing 3 of 6 website sections for a total of 30 minutes. The pretest/posttest was administered immediately before and after the intervention. Participants completed a second posttest via telephone 3 weeks thereafter to assess knowledge retention, attitudes, and use of the website. RESULTS: Sixty-three patients participated (96% participation rate). Website exposure was associated with a mean 17.1% same day knowledge score increase between pretest and posttest (P < .001). At 3 weeks, participants' knowledge scores remained 11.7% above pretest (P < .001). The greatest knowledge gain from pretest to 3-week follow-up occurred in the Treatment Options (P < .0001) and Cultural Beliefs and Myths (P < .0001) website sections. Most participants (95%) "agreed" or "strongly agreed" that they would recommend the website to other Hispanics. CONCLUSIONS: Web-based education for patients undergoing dialysis can effectively increase Hispanics' knowledge about transplantation and living kidney donation. Study limitations include small sample size and single geographic region study. Dialysis facilities could enable website access as a method of satisfying policy requirements to provide education about kidney transplantation.

Combined hepatocellular-cholangiocarcinoma (cHCC-CC): a distinct entity.

Patients with hepatocellular carcinoma (HCC), the fifth most common cancer worldwide, display a highly variable clinical course, suggesting that HCC encompasses several biologically distinct subtypes. This heterogeneity has the potential to impede both treatment decisions and prognostic predictions for patients with HCC. One distinct, albeit rare, subtype of HCC is combined hepatocellular-cholangiocarcinoma (cHCC-CC), which overall carries a poorer prognosis than HCC and cholangiocarcinoma (CC) alone. This review discusses predominantly the histopathologic and pathogenetic intricacies of this tumor and highlights the need for an accurate diagnosis of this specific HCC subtype.

Hispanic/Latino concerns about living kidney donation: a focus group study.

CONTEXT: Given the shortage of kidneys for transplant, living kidney donation (LKD) is increasingly used to expand the organ donor pool. Although Hispanics/Latinos need disproportionately more kidney transplants, they receive a smaller proportion of living donor kidney transplants than other ethnic/racial groups. OBJECTIVE: To assess Hispanics' awareness, perceptions, misconceptions, cultural beliefs, and values about and barriers to LKD. DESIGN: Nine focus groups were conducted with 76 adult Hispanics in Chicago, Illinois, between January and March 2012. PARTICIPANTS: Focus groups included kidney transplant recipients, living kidney donors, dialysis patients, and the general Hispanic public. RESULTS: Several themes emerged as perceived barriers to LKD. Many participants identified knowledge deficits about LKD, expressing uncertainty about the differences between LKD and deceased donation, and whether kidney disease simultaneously afflicts both kidneys. Many believed that donors experience dramatically shorter life expectancies, are unable to have children, and are more susceptible to kidney disease after donating. Recipients and donors reported that family members were involved in discussions about the donor's decision to donate, with some family members discouraging donation. Financial barriers cited included fear of becoming unable to work, losing one's job, or being unable to pay household bills while recovering. Participants also identified logistic barriers for undocumented immigrants (eg, the inability to obtain government insurance for transplant candidates and uncertainty about their eligibility to donate). Donors desired information about optimizing self-care to promote their remaining kidney's health. Culturally competent interventions are needed to redress Hispanics' knowledge deficits and misconceptions and reduce LKD disparities among Hispanics.

Mucoepidermoid carcinoma of lung masquerading as urothelial carcinoma of bladder.

BACKGROUND: Mucoepidermoid carcinoma (MEC) of the lung is a rare subtype of non-small cell lung cancer. There is no consensus regarding optimal management for this disease. CASE REPORT: We present a case of MEC of the lung in a 75 year-old female with a history of superficial urothelial carcinoma of the bladder. The patient was found to have an asymptomatic lung mass. Initial biopsy suggested metastatic recurrence of urothelial carcinoma and therefore, cisplatin and gemcitabine chemotherapy was administered prior to surgical resection. Pathological analysis of the resected specimen confirmed a diagnosis of stage IIIA MEC with focal high-grade features including transitional cell-like areas. Adjuvant radiotherapy was administered due to a positive microscopic resection margin. No chemotherapy was given due to lack of supporting data. The patient developed widespread metastatic disease 3 months following completion of radiotherapy and died 1 month later. CONCLUSION: This case demonstrates the possibility of dual pathology in cases where metastatic disease is suspected. The use of small tissue samples may complicate diagnosis due to the heterogeneity of malignant tumours.

Co-design with Integrated Care Teams: Establishing Information Needs.

Introduction: Co-design has been cited as playing a major role in the future of effective integrated care, however, there is a lack of reporting and reflection on the methods used. Information sharing is fundamental when working in integrated care, however sharing across professions, service settings and localities can be complex. Through co-design, we seek to establish a shared understanding of information needs within a newly formed integrated care team. In doing so we aim to inform future practice in the understanding of co-design. Description: Co-design Workshop 1 (N = 24 participants, plus 6 facilitators), collected 'Current Position' understanding of service information needs. Co-design Workshop 2 (N = 18 participants, plus 6 facilitators) sought a 'Future Position' understanding, identifying solutions and next steps for establishing information-need solutions. Reflection on the co-design process was conducted to inform future co-design practices. Conclusion: Identified was a wide range of future service information needs under the themes of Culture Building, Health System Needs, and Processes. We conclude with 4 key learning points on co-designing. 1. Ensure simplicity in format. 2. Interdisciplinary co-design and co-facilitation of workshops are beneficial. 3. Planning and preparation are key. 4. Co-designing can enhance communication for service improvement.

The translating bacterial ribosome at 1.55 Å resolution generated by cryo-EM imaging services.

Our understanding of protein synthesis has been conceptualised around the structure and function of the bacterial ribosome. This complex macromolecular machine is the target of important antimicrobial drugs, an integral line of defence against infectious diseases. Here, we describe how open access to cryo-electron microscopy facilities combined with bespoke user support enabled structural determination of the translating ribosome from Escherichia coli at 1.55 Å resolution. The obtained structures allow for direct determination of the rRNA sequence to identify ribosome polymorphism sites in the E. coli strain used in this study and enable interpretation of the ribosomal active and peripheral sites at unprecedented resolution. This includes scarcely populated chimeric hybrid states of the ribosome engaged in several tRNA translocation steps resolved at ~2 Å resolution. The current map not only improves our understanding of protein synthesis but also allows for more precise structure-based drug design of antibiotics to tackle rising bacterial resistance.

Racialization and Reproduction: Asian Immigrants and California's Twentieth-Century Eugenic Sterilization Program.

During the twentieth century, state health authorities in California recommended sterilization for over 20,000 individuals held in state institutions. Asian immigrants occupied a marginalized position in racial, gender, and class hierarchies in California at the height of its eugenic sterilization program. Scholars have documented the disproportionate sterilization of other racialized groups, but little research exists connecting the racist, gendered implementation of Asian immigration restriction to the racism and sexism inherent in eugenics. This study examines patterns of coercive sterilization in Asian immigrants in California, hypothesizing higher institutionalization and sterilization rates among Asian-born compared with other foreign- and US-born individuals. We used complete count census microdata from 1910 to 1940 and digitized sterilization recommendation forms from 1920 to 1945 to model relative institutionalization and sterilization rates of Asian-born, other foreign-born, and US-born populations, stratified by gender. Other foreign-born men and women had the highest institutionalization rates in all four census years. Sterilization rates were higher for Asian-born women compared with US-born [Incidence Rate Ratio (IRR) = 2.00 (95% CI: 1.61, 2.48)] and other foreign-born women (p < 0.001) across the entire study period. Sterilization rates for Asian-born men were not significantly higher than those of US-born men [IRR 0.95 (95% CI 0.83, 1.10). However, an inflection point model incorporating the year of sterilization found higher sterilization rates for Asian-born men than for US-born men prior to 1933 [IRR 1.31 (95% CI 1.09, 1.59)]. This original quantitative analysis contributes to the literature demonstrating the health impact of discrimination on Asian-Americans and the disproportionate sterilization of racial minorities under state eugenics programs.

IL28B, HLA-C, and KIR variants additively predict response to therapy in chronic hepatitis C virus infection in a European Cohort: a cross-sectional study.

BACKGROUND: To date, drug response genes have not proved as useful in clinical practice as was anticipated at the start of the genomic era. An exception is in the treatment of chronic hepatitis C virus (HCV) genotype 1 infection with pegylated interferon-alpha and ribavirin (PegIFN/R). Viral clearance is achieved in 40%-50% of patients. Interleukin 28B (IL28B) genotype predicts treatment-induced and spontaneous clearance. To improve the predictive value of this genotype, we studied the combined effect of variants of IL28B with human leukocyte antigen C (HLA-C), and its ligands the killer immunoglobulin-like receptors (KIR), which have previously been implicated in HCV viral control. METHODS AND FINDINGS: We genotyped chronic hepatitis C (CHC) genotype 1 patients with PegIFN/R treatment-induced clearance (n = 417) and treatment failure (n = 493), and 234 individuals with spontaneous clearance, for HLA-C C1 versus C2, presence of inhibitory and activating KIR genes, and two IL28B SNPs, rs8099917 and rs12979860. All individuals were Europeans or of European descent. IL28B SNP rs8099917 "G" was associated with absence of treatment-induced clearance (odds ratio [OR] 2.19, p = 1.27×10(-8), 1.67-2.88) and absence of spontaneous clearance (OR 3.83, p = 1.71×10(-14), 2.67-5.48) of HCV, as was rs12979860, with slightly lower ORs. The HLA-C C2C2 genotype was also over-represented in patients who failed treatment (OR 1.52, p = 0.024, 1.05-2.20), but was not associated with spontaneous clearance. Prediction of treatment failure improved from 66% with IL28B to 80% using both genes in this cohort (OR 3.78, p = 8.83×10(-6), 2.03-7.04). There was evidence that KIR2DL3 and KIR2DS2 carriage also altered HCV treatment response in combination with HLA-C and IL28B. CONCLUSIONS: Genotyping for IL28B, HLA-C, and KIR genes improves prediction of HCV treatment response. These findings support a role for natural killer (NK) cell activation in PegIFN/R treatment-induced clearance, partially mediated by IL28B.

From Recoding to Peptides for MHC Class I Immune Display: Enriching Viral Expression, Virus Vulnerability and Virus Evasion.

Many viruses, especially RNA viruses, utilize programmed ribosomal frameshifting and/or stop codon readthrough in their expression, and in the decoding of a few a UGA is dynamically redefined to specify selenocysteine. This recoding can effectively increase viral coding capacity and generate a set ratio of products with the same N-terminal domain(s) but different C-terminal domains. Recoding can also be regulatory or generate a product with the non-universal 21st directly encoded amino acid. Selection for translation speed in the expression of many viruses at the expense of fidelity creates host immune defensive opportunities. In contrast to host opportunism, certain viruses, including some persistent viruses, utilize recoding or adventitious frameshifting as part of their strategy to evade an immune response or specific drugs. Several instances of recoding in small intensively studied viruses escaped detection for many years and their identification resolved dilemmas. The fundamental importance of ribosome ratcheting is consistent with the initial strong view of invariant triplet decoding which however did not foresee the possibility of transitory anticodon:codon dissociation. Deep level dynamics and structural understanding of recoding is underway, and a high level structure relevant to the frameshifting required for expression of the SARS CoV-2 genome has just been determined.

Elexacafator/tezacaftor/ivacaftor resolves subfertility in females with CF: A two center case series.

Infertility and subfertility are commonly faced by females with cystic fibrosis (FwCF) and resulting in decreased contraceptive use and increased utilization of reproductive technologies. Elexacaftor-tezacaftor-ivacaftor (ETI) is a CFTR modulator that affects common causes of subfertility. Two CF centers conducted a retrospective chart review on females with CF who were receiving ETI and became pregnant. We analyzed obstetrical-gynecological history, genotype, and clinical response to ETI therapy. Fourteen FwCF on ETI became pregnant. Half (7) of the FwCFs were previously attempting to conceive, but only three were using contraceptives. Four FwCF had a history of infertility; two were reconsidering use of reproductive technologies (IUI). Patients achieved conception at mean 8 weeks after initiating ETI. ETI may lessen CF-associated factors that affect fertility; however, its exact mechanism is unknown. This warrants counseling on contraceptive use and family planning prior to initiation of therapy and at routine intervals while utilizing ETI.