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Background: Seasonal influenza is prevented through annual vaccination, especially in children and older adults. These vaccines are annually updated based on World Health Organization recommendations and require continuous safety monitoring., Objective: We assessed the frequency and severity of adverse events within 7 days of administering GSK's inactivated quadrivalent seasonal influenza vaccine (IIV4) in Belgium, Germany, and Spain during the 2022/2023 influenza season., Methods: In this enhanced safety surveillance study, adults who received GSK's IIV4 and parents/guardians/legally acceptable representatives of vaccinated children (aged 6 months-17 years) were invited to complete adverse drug reaction cards reporting adverse events within 7 days post-vaccination., Results: In total, 1332 participants (53.6% female) received at least one dose of GSK's IIV4, including 43 children who received two doses. Overall, 97.8% of adverse drug reaction cards were completed and returned in the study. All participants in Belgium were adults, while 54.7% and 7.4% in Spain and Germany, respectively, were pediatric participants aged 6 months-17 years. After Dose 1, across all age groups, 49.8% of participants reported at least one adverse event. The most common adverse events (cumulative frequency >5%) following Dose 1 were injection-site pain (37.6%), fatigue (15.0%), headache (13.2%), injection-site swelling (9.3%), myalgia (7.6%), and injection-site erythema (7.4%). Across all countries, adverse events were most common in adults aged 18-65 years (59.7%), followed by those aged 3-17 years (47.0%), >65 years (35.7%), and 6-35 months (23.5%). After Dose 2, 18.6% of participants reported at least one adverse event, with general disorders and administration site conditions again being the most frequent., Conclusions: Across all age and risk groups for serious disease, no serious adverse events related to GSK's IIV4 were reported within 7 days post-vaccination. This study supports and confirms the acceptable safety profile of GSK's IIV4 across all recommended age groups., Clinical Trial Registration: ClinicalTrials.gov number: not applicable., (© 2024. GSK.)

Objectives: To compare vaccine-related attitudes and values of parents of children 2-17 years old to other adults, examine intentions to vaccinate their children, and identify factors associated with intending to vaccinate children., Methods: A nationally representative survey was conducted in September 2021 (just before the EUA for children 5-11 years old) using Ipsos KnowledgePanel, a probability-based web panel. The survey measured COVID-19 vaccination status, intentions, attitudes, values, and trust in public health authorities among US adults. Scale response options to survey items were dichotomized, and cross-tabulations and logistic regressions were performed., Results: Parents had lower odds of reporting being vaccinated against COVID-19 than other adults even after adjusting for associated sociodemographic characteristics such as age (aOR: 0.66; 95 %CI: 0.50-0.87). The most prevalent parental concerns about COVID-19 vaccines included the speed of their development (88 %), potential side effects (78 %), suspicion of government (77 %), and suspicion of pharmaceutical companies (72 %). Fewer than half (42 %) of parents intended to vaccinate their children 5-11 years old, while 38 % were uncertain and 20 % were unlikely to ever vaccinate their children. Vaccinated parents had higher odds than unvaccinated parents of intending to vaccinate their children (OR: 675.51; 95 %CI: 106.46-4286.12). Discussions with healthcare providers who encouraged COVID-19 vaccination were positively associated with intent to vaccinate children (OR: 11.29; 95 %CI: 2.60-49.02)., Conclusions: We found parental vaccination and conversations with providers were positively associated with intent to vaccinate children. Decisions about childhood vaccination need to be supported by healthcare providers and a public health system that makes vaccine access and related information equitable and accessible. Vaccination-related decision making should be guided by healthcare providers and provide information about safety and risk to children., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Matthew Dudley has received research support from Merck. Daniel Salmon has received research support from Merck and serves on advisory boards for Merck, Janssen, Sanofi and Moderna. Matthew Dudley, Daniel Salmon, and Rajiv Rimal have received funding from the Vaccination Confidence Fund, which is jointly funded by Facebook and Merck. Jennifer Gerber has received support from RTI International. All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: This scoping review summarizes a key aspect of vaccinomics by collating known associations between heterogeneity in human genetics and vaccine immunogenicity and safety., Methods: We searched PubMed for articles in English using terms covering vaccines routinely recommended to the general US population, their effects, and genetics/genomics. Included studies were controlled and demonstrated statistically significant associations with vaccine immunogenicity or safety. Studies of Pandemrix®, an influenza vaccine previously used in Europe, were also included, due to its widely publicized genetically mediated association with narcolepsy., Findings: Of the 2,300 articles manually screened, 214 were included for data extraction. Six included articles examined genetic influences on vaccine safety; the rest examined vaccine immunogenicity. Hepatitis B vaccine immunogenicity was reported in 92 articles and associated with 277 genetic determinants across 117 genes. Thirty-three articles identified 291 genetic determinants across 118 genes associated with measles vaccine immunogenicity, 22 articles identified 311 genetic determinants across 110 genes associated with rubella vaccine immunogenicity, and 25 articles identified 48 genetic determinants across 34 genes associated with influenza vaccine immunogenicity. Other vaccines had fewer than 10 studies each identifying genetic determinants of their immunogenicity. Genetic associations were reported with 4 adverse events following influenza vaccination (narcolepsy, GBS, GCA/PMR, high temperature) and 2 adverse events following measles vaccination (fever, febrile seizure)., Conclusion: This scoping review identified numerous genetic associations with vaccine immunogenicity and several genetic associations with vaccine safety. Most associations were only reported in one study. This illustrates both the potential of and need for investment in vaccinomics. Current research in this field is focused on systems and genetic-based studies designed to identify risk signatures for serious vaccine reactions or diminished vaccine immunogenicity. Such research could bolster our ability to develop safer and more effective vaccines., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Dr. Dudley reports research support from Walgreens and Merck. Dr. Gerber reports support for manuscript revisions from RTI International. Dr. Salmon reports consulting and/or research support from Walgreens, Merck, and Janssen. Dr. Poland is the chair of a Safety Evaluation Committee for novel investigational vaccine trials being conducted by Merck Research Laboratories. Dr. Poland offers consultative advice on vaccine development to Merck & Co., Medicago, GlaxoSmithKline, Sanofi Pasteur, Emergent Biosolutions, Dynavax, Genentech, Eli Lilly and Company, Janssen Global Services LLC, Kentucky Bioprocessing, and Genevant Sciences, Inc. Dr. Poland holds patents related to vaccinia, influenza, and measles peptide vaccines. Dr. Poland has received grant funding from ICW Ventures for preclinical studies on a peptide-based COVID-19 vaccine. These activities have been reviewed by the Mayo Clinic Conflict of Interest Review Board and are conducted in compliance with Mayo Clinic Conflict of Interest policies. All other authors have no disclosures]., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The Delta COVID-19 variant caused a resurgence in cases and deaths during the summer of 2021, particularly among the unvaccinated, highlighting the need to increase vaccine coverage. We describe a survey conducted in September 2021, in the midst of the Delta variant surge, after the FDA fully approved Pfizer-BioNTech’s vaccine for ages 16+ and issued an emergency use authorization for ages 12−15. Methods and Findings: US adults were surveyed to measure COVID-19 vaccination status, intentions, attitudes, values, and trust in public health authorities. More than three-quarters (77%) reported receiving at least one dose of COVID-19 vaccination. Of the unvaccinated, 6% intended to vaccinate, 40% were unlikely to ever vaccinate, and 55% remained uncertain. Most of the unvaccinated were <45 years old (62%), without a bachelor’s degree (83%), earning less than $85,000 annually (74%), and Republican/Independent (66%). Concerns among the unvaccinated-yet-still-uncertain included the vaccines’ safety (86%), speed of development (86%), and suspicion of government (79%) and pharmaceutical companies (69%). Most (86%) of the unvaccinated reported they would not vaccinate if mandated by their employer. About one third (34%) of the unvaccinated reported facing at least one barrier to vaccination. Conclusion: More than half of unvaccinated adults remained uncertain about COVID-19 vaccination, indicating an opportunity to support their decision making. Public health must increase easy and equitable access to vaccination and renew efforts to provide unvaccinated populations access to information from trusted sources.

Objective : We characterize public values regarding vaccinomics, which aims to improve vaccine safety and effectiveness using genomics. Methods: Panel survey (2020) of ≥18-year-olds with embedded animation introduced vaccinomics. Sociodemographic, health, and vaccination-related items were adapted from validated scales. Novel items measured trust in public health authorities, vaccinomics-related values, and preferences for federal funding: vaccinomics compared with vaccine issues and chronic diseases. Beginning and end of survey confidence in vaccine safety was measured to assess potential changes. Data were weighted to the U.S. Census. Vaccinomics-related concerns were stratified by sociodemographic characteristics, vaccine hesitancy status (composite outcome), reported serious vaccine reactions, and trust in public health authorities (PHA). Log binomial regression models estimated associations between these variables and agency to make vaccine-related decisions. Results: Most (70.7%, N = 1,925) respondents expected vaccinomics would increase their vaccine confidence compared to now. Agreement was highest among those without serious vaccine reaction experience (unexperienced: 74.2% versus experienced: 62.3%), with high trust in PHA (high: 83.3% versus low: 57.4%), and low vaccine hesitancy among parents of teenagers (low: 78.8% versus high: 62.5%) and adults without minor children (low: 79.8% versus high: 60.6%; all p < .01). Belief that vaccination was an individual's choice was associated with reported serious reactions (adjusted Prevalence Ratio (aPR): 1.16; 95% CI: 1.07, 1.25) and low trust (aPR: 0.91; 0.84, 0.98). Beginning versus end of survey vaccine safety perceptions were similar. Conclusion: Federal funding, communications, and policies should assure the public that vaccinomics will not remove their decision-making power and engender trust in PHA.

Objectives : We aimed to elucidate public values regarding the use of genomics to improve vaccine development and use (vaccinomics). Methods : Adults ≥18 years-old were recruited through social media and community organizations, and randomly assigned to one of four nested discussion groups in Boulder, CO and Baltimore, MD. Participants rated their confidence in vaccine safety and effectiveness prior to and after discussing vaccinomics. Before departing, they prioritized funding for vaccinomics versus federal priorities (vaccine safety and efficacy, new vaccines, and free vaccines) and chronic diseases (cancer, heart disease, and diabetes). Grounded Theory-influenced methods were used to identify themes. Results : Participants broadly supported vaccinomics. Emergent themes: concerns about reduced privacy/confidentiality, increased genetically based stigma/discrimination, and reduced agency to make vaccine-related decisions through genetically based prioritization. Participants supported vaccinomics' potential for increased personalization. Some participants favored prioritizing others over themselves during a vaccine shortage, while others did not. Some participants worried health insurance companies would discriminate against them based on information discovered through vaccinomics. Participants feared inequitable implementation of vaccinomics would contribute to discrimination and marginalization of vulnerable populations. Discussing vaccinomics did not impact perceptions of vaccine safety and effectiveness. Federal funding for vaccinomics was broadly supported. Conclusion : Participants supported vaccinomics' potential for increased personalization, noting policy safeguards to facilitate equitable implementation and protect privacy were needed. Despite some concerns, participants hoped vaccinomics would improve vaccine safety and effectiveness. Policies regarding vaccinomics' implementation must address public concerns about the privacy and confidentiality of genetic information and potential inequities in access to vaccinomics' benefits.

Introduction: Safe and effective vaccines against Coronavirus Disease 2019 (COVID-19) provide the best opportunity to control the pandemic. Having safe and efficacious vaccines available is only half the equation; people must also take them. We describe a study to identify COVID-19 vaccine attitudes, values and intentions immediately preceding authorization of COVID-19 vaccines in the US., Methods: A national panel survey was conducted to measure intent to receive COVID-19 vaccines as well as disease and vaccine attitudes, values and trust in local, state and federal public health authorities., Results: Greater than 80% of respondents reported confidence they could adhere to COVID recommendations such as mask wearing, social distancing and hand washing. The majority of respondents (70%) reported believing that current drugs were somewhat or very good at treating COVID-19 infection. Vaccine intent fell into three groups: Intenders (50%), Wait and Learn (40%), and Unlikelys (10%). Intent to get vaccinated was substantially lower among African American (32%), and higher among men (56%), those over 60 years of age (61%), those with a Bachelor's degree or higher (63%), and Democrats (63%). The Wait and Learn group, compared to the Intenders, were less likely to report being diagnosed with a high risk condition for COVID-19, receiving an influenza vaccine in the past 12 months, discussing COVID-19 vaccine with their healthcare provider, perceiving COVID-19 as severe, considering a COVID-19 vaccine important to stop the spread of infection, and wering a mask usually or almost always., Conclusion: Only half of US adults intend to accept COVID-19 vaccines; most others (40%) are uncertain. Levels of immunity associated with community protection will not be achieved without reaching those who are currently uncertain. Characterizing COVID-19 vaccine attitudes and intentions and ascertaining values and trust in local, state, and federal public health authorities that impact vaccine decision-making are essential., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The impact of host genomics on an individual's susceptibility, immune response, and risk of severe outcomes for a given infectious pathogen is increasingly recognized. As we uncover the links between host genomics and infectious disease, a number of ethical, legal, and social issues need to be considered when using that information in clinical practice or workforce decisions. We conducted a survey of the clinical staff at 10 federally funded Regional Ebola and Other Special Pathogen Treatment Centers to understand their views regarding the ethical, legal, and social issues related to host genomics and the administrative and clinical functions of high-level isolation units. Respondents overwhelmingly agreed that genomics could provide valuable information to identify patients and employees at higher risk for poor outcomes from highly infectious diseases. However, there was considerable disagreement about whether such data should inform the allocation of scarce resources or determine treatment decisions. While most respondents supported a confidential employer-based genomic testing system to inform individual employees about risk, respondents disagreed about whether such information should be used in staffing models. Respondents who thought genomic information would be valuable for patient treatment were more willing to undergo genetic testing for staffing purposes. Most respondents felt they would benefit from additional training to better interpret results from genetic testing. Although this study was completed before the COVID-19 pandemic, the responses provide a baseline assessment of provider attitudes that can inform policy during the current pandemic and in future infectious disease outbreaks.

Infectious disease outbreaks highlight the importance of trust in public health authorities to avoid fear and improve adherence to recommendations. There is currently no established and validated measure for trust in public health authorities. We aimed to develop and validate an instrument that measures trust in public health authorities and to assess the association between trust in public health authorities and vaccine attitudes. We developed 20 items to measure trust in public health authorities. After implementing a survey in January 2020, we investigated relationships between the items, reduced the number of items, and identified latent constructs of the scale. We assessed variability in trust and how trust was associated with vaccine attitudes, beliefs, and self-reported vaccine acceptance. The pool was reduced to a 14-item trust in public health authorities scale and we found that this trust model was strongly associated with acceptance of vaccines. Our scale can be used to examine the relationship between trust in public health authorities and adherence to public health recommendations. The measure needs to be validated in other settings to determine whether they are associated with other areas where the public question public health authority recommendations.

Importance: Human papillomavirus-related oropharyngeal carcinoma (HPV-OPC) is increasing in incidence in the United States. Although HPV-OPC has favorable prognosis, 10% to 25% of HPV-OPCs recur. Detection of human papillomavirus (HPV) DNA in oral rinses is associated with HPV-OPC, but its potential as a prognostic biomarker is unclear., Objective: To determine whether HPV DNA detection in oral rinses after treatment for HPV-OPC is associated with recurrence and survival., Design, Setting, and Participants: Prospective cohort study of patients with incident HPV-OPC diagnosed from 2009 to 2013 at 4 academic tertiary referral cancer centers in the United States. Oral rinse samples were collected at diagnosis and after treatment (9, 12, 18, and 24 months after diagnosis), and evaluated for HPV DNA. Among an initial cohort of 157 participants with incident HPV-OPC treated with curative intent, 124 had 1 or more posttreatment oral rinses available and were included in this study., Main Outcomes and Measures: Disease-free survival (DFS) and overall survival (OS) were estimated by the Kaplan-Meier method, and the association of HPV DNA detection in oral rinses with survival was evaluated using Cox regression analysis., Results: Oral HPV type 16 (HPV16) DNA was common at diagnosis (67 of 124 participants [54%]). In contrast, oral HPV16 DNA was detected in only 6 participants after treatment (5%), including 5 with HPV16 DNA also detected at diagnosis (persistent oral HPV16 DNA). Two-year DFS and OS were 92% (95% CI, 94%-100%) and 98% (95% CI, 93%-99%). Persistent oral HPV16 DNA was associated with worse DFS (hazard ratio, 29.7 [95% CI, 9.0-98.2]) and OS (hazard ratio, 23.5 [95% CI, 4.7-116.9]). All 5 participants with persistent oral HPV16 DNA developed recurrent disease, 3 with local disease involvement. In contrast, just 9 of 119 participants (8%) without persistent oral HPV16 DNA developed recurrent disease, only 1 (11%) with local disease involvement. Median (range) time from earliest posttreatment oral HPV16 DNA detection to recurrence was 7.0 (3.7-10.9) months., Conclusions and Relevance: Human papillomavirus type 16 DNA in oral rinses is common at diagnosis but rare after treatment for HPV-OPC. Our data suggest that, although infrequent, persistent HPV16 DNA in posttreatment oral rinses is associated with poor prognosis and is a potential tool for long-term tumor surveillance, perhaps more so for local recurrence.

Objectives: We hypothesized that viral and host factors impact the serologic responses to HPV early antigens in HPV-positive oropharyngeal cancer (HPVOPC)., Materials and Methods: We conducted a multicenter study to measure HPV16-specific IgG among patients with HPVOPC, their long-term sexual partners, and healthy volunteers. Risk factor surveys and rinse and gargle specimens were collected. Peripheral blood samples at diagnosis were evaluated for IgG Abs to HPV16 antigens using a programmable ELISA assay. Predictors for HPV16 serologic responses were evaluated using univariate and multivariable linear regression., Results: 116 patients with HPVOPC, 43 partners, and 81 healthy volunteers were enrolled and had baseline sera for analysis. Cases were primarily male (90%), with a median age of 56 years. Abs to E1, E2, E6 or E7 antigens were detected more often in HPVOPC compared with volunteers or partner sera (p<0.0001). HPV16 Abs to at least one early protein (E1, E2, E4, E5, E6, or E7) were detected in the sera of 90.6% of cases, 0% of partners and 7.4% of healthy volunteers. Gender, race, sexual behavior, and viral integration were not associated with antibody response. Younger age and higher oral HPV16 copy number were associated with higher HPV16 E6 and NE2 antibody levels., Conclusions: HPV16 seroreactivity is commonly detected among patients with HPVOPC at diagnosis, but not among partners or healthy volunteers. Seroreactivity among cases are correlated with viral load and stage and not with other demographic or behavioral factors. Positive HPV16 serology was strongly associated with HPV 16 oropharyngeal cancer., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Epstein-Barr virus (EBV) infection is widely considered to be a risk factor for multiple sclerosis (MS). A previous meta-analysis estimated an odds ratio (OR) for MS in individuals seronegative for EBV of 0.06. Given the potential importance of this finding, we aimed to establish a more precise OR for adult and paediatric onset MS in EBV seronegative individuals., Methods: PubMed and EMBASE searches were undertaken to identify studies investigating the association between MS and EBV. Twenty-two adult and three paediatric studies were included. ORs were calculated using a fixed effects model. A sub-group analysis based on the method of EBV detection was performed., Results: The OR for developing adult MS in EBV seronegatives was 0.18 (95% confidence interval (CI) 0.13-0.26)) and for paediatric MS was 0.18 (95% CI 0.11-0.30). Sub-group analysis on EBV detection method showed that studies which used immunofluoresence generated an OR=0.07 (95% CI 0.03-0.16); for those that used enzyme-linked immunosorbent assay (ELISA) OR=0.33 (95% CI 0.22-0.50) and for studies which used ELISA and immunofluoresence OR=0.00 (95% CI 0-0.43)., Conclusion: The sensitivity and specificity of the assay used to measure EBV antibody titres have an influence on the association between MS and EBV. Looking at studies where two independent methods are used and therefore are likely to be the most robust, EBV appears to be present in 100% of MS patients. This has implications for future studies of EBV in MS. MS patients without EBV infection, if they truly exist, should be studied in more detail.

Bacterial infection due to Bartonella henselae commonly develops in children and young adults following cat/dog contacts and/or cat/dog scratches. Regional lymphadenopathy is its most common clinical expression. However, encephalitis and Parinaud's syndrome (oculoglandular syndrome) have also been reported as has systemic illness. A review of the international literature in all languages revealed no fatal complications in immunocompetent hosts. A four-year-old white child with no underlying illness began to have seizure-like activity. She was taken to a local hospital and subsequently transferred to a medical center. The child was treated aggressively for seizures and fever of unknown origin. However, her condition rapidly declined and she died without a specific diagnosis. At autopsy there was marked cerebral edema with no gross evidence of acute meningitis. Microscopic exams revealed multiple granulomatous lesions as well as a meningitis and encephalitis. A variety of cultures and stains were negative for acid fast and fungal organisms. Warthin-Starry stains of involved tissue including brain and liver revealed pleomorphic rod shaped bacilli consistent with Barronella henselae. Analysis of brain tissue with polymerase chain reaction (PCR) and Southern blot for the deoxyribonucleic acid (DNA) was definitive for DNA of Bartonella henselae bacteria.

Bacterial infection with Clostridium perfringens in children less than 2 years of age is frequently associated with meningitis, necrotizing gastrointestinal infection, and postoperative infections. However, a review of the literature reveals no reports of these bacteria infecting the tonsils. A 9-month old black female was found unresponsive at the baby-sitter's and was rushed to the hospital. Shortly after admission to the emergency department death was pronounced. An autopsy performed on this otherwise healthy infant revealed shock and acute necrotizing bacterial tonsillitis. The initial report of this infant's death was questionable sudden infant death syndrome and questionable smothering. Postmortem cerebrospinal fluid, blood, and lung cultures grew pure colonies of C. perfringens. The necrotizing tonsil revealed no significant gross lesions. Microscopically, large numbers of gram-positive rods were easily recognized and were compatible with C. perfringens. Because the oropharynx is a common portal of entry for infectious agents, it is essential to sample tissues of Waldeyer's ring and especially the tonsils to find infectious diseases that may become systemic.

Deaths resulting from the oral ingestion of colchicine are occasionally associated with suicides and therapeutic toxicity. However, homicidal deaths in which this drug is used are extremely rare. Two homicides in which colchicine was used are reported.

Olanzapine is an antipsychotic drug that has been on the market since 1996. Olanzapine-related deaths are very rare; the literature reports only one. However, in a recent 5-month period one medical examiner's office found two such cases that are reported in this paper. One is a suicide and the other is not. The toxicologic and anatomic findings for each are described. Blood olanzapine concentrations ranged from 0.237 microg/ml for one to 0.675 microg/ml for the other. Gastric content concentrations also exhibited a wide range, varying from 0.197 microg/ml to 17.400 microg/ml for the other. Distribution studies of the liver, kidney, and brain produced nondetectable concentrations for the drug. There were no consistent pathologic anatomic findings for cause of death except for moderate coronary atherosclerosis in the nonsuicide case. Both deaths were attributed to olanzapine toxicity.

The homologous nature and morphological similarities between cutaneous and salivary gland tumors have been well documented. This is especially true of the monomorphic adenoma, eccrine spiradenoma and cylindroma. Prior to the first full clinical and pathological description, about twenty-five years ago, the lesion of eccrine spiradenoma had been given multiple synonyms. This report is of a patient with an eccrine spiradenoma in the buttock and dermaltype cylindroma of the parotid gland. This may represent the transformation of pleuripotential basal cells originating in the parotid and eccrine sweat gland.

The gall bladder mucosa is composed of neutral mucopolysaccharide and protein radical containing secretory cells, protein radical containing migratory cells, and neutral and acid mucopolysaccharides plus sialic acid containing goblet cells. The prognostic significance of histologic or histochemical parameters in gall bladder adenocarcinoma (GBA) are unknown. To determine if histochemical acid mucopolysaccharide content in GBA has prognostic value, GBA histologic sections from 26 advanced stage disease patients participating in Eastern Cooperative Oncology Group (ECOG) treatment study EST-2273 were stained with alcian blue at pH. 1.0, assessed by a pathology panel for either high (greater than 50%) or low (less than 50%) acid mucopolysaccharide content, and correlated with patient survival. Initial panel unanimous concurrence rate on acid mucopolysaccharide content was 88.9%. Median survival times from the start of chemotherapy to date of death for high acid mucopolysaccharide content GBA was 14 weeks versus five weeks for the low content GBA (P less than 0.0001). The results indicate that high acid mucopolysaccharide content in GBA significantly improves prognosis. ECOG recommends stratification by acid mucopolysaccharide content in future GBA treatment investigations.

Exflagellation of microgametocytes in malarial parasites is associated with the life cycle in the mosquito. However, it is not found with the usual developmental phases in humans. This report describes two case reports where exflagellation of microgametocytes was observed in vitro in patients documented to have Plasmodium vivax malaria.

A case of fibrous hamartoma of infancy occurring in the scalp of a 14-month-old is described. Light microscopy revealed features similar to those described previously. Electron microscopic studies revealed cells with ultrastructural characteristics of both fibroblasts and possibly myofibroblasts. In addition, occasional fusiform banded fibers (Luse bodies) were identified. This is the first reported case of a fibrous hamartoma of infancy in the scalp and the first description of its ultrastructural features.

Gallbladder adenocarcinoma (GBA) postresection 5-year survival rates are less than 5%, but when histologically confined to the mucosa or submucosa, survival rates of 64% (5 years) and 44% (10 years) have been reported. Whether any other histologic features of GBA have prognostic significance is unknown. This investigation was conducted to determine if GBA histologic grade correlates with survival. Thirty patients with advanced stage GBA participating in Eastern Cooperative Oncology Group (ECOG) treatment protocol EST-2273 served as the study material. Using glandular tumor grade criteria recommended by others, a panel of 7 ECOG pathologists categorized the GBA as either predominantly low or high histologic grade. Each patient's GBA histologic section measured no less than 1.0 X 1.0 cm. Predominant grade was defined as being that grade present in greater than 75% of the histologic section. Patient survival times by grade were calculated from date of initiation of chemotherapy until date of death. The 13-week low grade GBA patient survival was significantly longer than the 7-week high grade GBA patient survival (p less than 0.01). Stratification of patients by either high or low predominant histologic grade is recommended in future GBA treatment studies.

One hundred four autopsy cases with previously diagnosed pneumonitis were examined for evidence of Legionnaires' disease. The peak epidemic months of July, August, and September in the five years before the 1977 Vermont epidemic were chosen for study. The bacterium, Legionella pneumophila (serogroup 1) was demonstrated in lung tissue by direct immunofluorescence and the Dieterle silver impregnation stain. There was no clustering of Legionnaires' disease in any one year., The clinical presentation and pulmonary pathology were similar to that of Legionnaires' disease previously reported in Vermont. Seven out of 104 cases were identified as previously undiagnosed Legionnaire's disease. In this time frame, it can be concluded that the disease has been endemic in Vermont.

Gastric adenocarcinoma developed in two young patients following successful radiation therapy and chemotherapy for malignant lymphoma in childhood. The age of presentation with gastric cancer, 14 years and 24 years, respectively, is so strikingly different from that expected as to suggest a causal relationship. Gastric adenocarcinoma may be another complication of the "successful" aggressive management of malignant tumors in young people.

Histological studies provide evidence that the bronchial veins are a site of leakage in histamine-induced pulmonary edema, but the physiological importance of this finding is not known. To determine if a lung perfused by only the bronchial arteries could develop pulmonary edema, we infused histamine for 2 h in anesthetized sheep with no pulmonary arterial blood flow to the right lung. In control sheep the postmortem extravascular lung water volume (EVLW) in both the right (occluded) and left (perfused) lung was 3.7 +/- 0.4 ml X g dry lung wt-1. Following histamine infusion, EVLW increased to 4.4 +/- 0.7 ml X g dry lung wt-1 in the right (occluded) lung (P less than 0.01) and to 5.3 +/- 1.0 ml X g dry wt-1 in the left (perfused) lung (P less than 0.01). Biopsies from the right (occluded) lungs scored for the presence of edema showed a significantly higher score in the lungs that received histamine (P less than 0.02). Some leakage from the pulmonary circulation of the right lung, perfused via anastomoses from the bronchial circulation, cannot be excluded but should be modest considering the low pressures in the pulmonary circulation following occlusion of the right pulmonary artery. These data show that perfusion via the pulmonary arteries is not a requirement for the production of histamine-induced pulmonary edema.