Transfusion-transmitted babesiosis in a patient with sickle cell disease undergoing chronic red cell exchange.

BACKGROUND: Prior to laboratory-based blood donor screening for Babesia, transfusion-transmitted babesiosis (TTB) was a leading infectious risk to the blood supply in the United States. CASE REPORT: A 30-year-old man with sickle cell disease (SCD) who had been on a chronic automated red cell exchange (RCE) regimen since childhood, presented approximately 2 months after an RCE, with fever, neck pain, and photophobia. Meningitis was excluded, and he was discharged. He presented again 2 days later with persistent fever, chills, headache, fatigue, and loss of appetite. RESULTS: On examination, the patient was febrile but hemodynamically stable. Intra-erythrocytic inclusions were identified on a peripheral blood smear (<0.5%). B. microti IgM and IgG titers were >1:320 (Reference <1:20) >1:1024 (Reference <1:64), respectively. B. microti was confirmed by nucleic acid testing. The patient lived in a Babesia endemic state but had no risk factors for tick-borne acquisition. Of the 65 units he received in the preceding 6 months, 58 had been screened for Babesia. One of the donors of the 7 untested units was B. microti seropositive (titer 1:128; Reference 1: 64). The donor was asymptomatic and resided in a state in which Babesia screening was not required. He reported traveling in the year before his donation. CONCLUSION: Although rare, TTB is still possible despite regional screening, underscoring the need for provider vigilance and education, especially in non-endemic areas. Patients with SCD are particularly vulnerable given their high frequency of transfusion and complex needs requiring blood procurement from states where Babesia screening is not mandatory.

Increased tumor-infiltrating lymphocyte density is associated with favorable outcomes in a comparative study of canine histiocytic sarcoma.

Histiocytic sarcoma (HS) is a rare and aggressive tumor in humans with no universally agreed standard of care therapy. Spontaneous canine HS exhibits increased prevalence in specific breeds, shares key genetic and biologic similarities with the human disease, and occurs in an immunocompetent setting. Previous data allude to the immunogenicity of this disease in both species, highlighting the potential for their successful treatment with immunotherapy. Quantification of CD3 tumor-infiltrating lymphocytes (TIL) in five cases of human HS revealed variable intra-tumoral T cell infiltration. Due to the paucity of human cases and lack of current model systems in which to appraise associations between anti-tumor immunity and treatment-outcome in HS, we analyzed clinical data and quantified TIL in 18 dogs that were previously diagnosed with localized HS and treated with curative-intent tumor resection with or without adjuvant chemotherapy. As in humans, assessment of TIL in biopsy tissues taken at diagnosis reveal a spectrum of immunologically "cold" to "hot" tumors. Importantly, we show that increased CD3 and granzyme B TIL are positively associated with favorable outcomes in dogs following surgical resection. NanoString transcriptional analyses revealed increased T cell and antigen presentation transcripts associated with prolonged survival in canine pulmonary HS and a decreased tumor immunogenicity profile associated with shorter survivals in splenic HS. Based on these findings, we propose that spontaneous canine HS is an accessible and powerful novel model to study tumor immunology and will provide a unique platform to preclinically appraise the efficacy and tolerability of anti-cancer immunotherapies for HS.

Assessing signs of torture: A review of clinical forensic dermatology.

BACKGROUND: It is important for dermatologists and other physicians in refugee-receiving countries to acquire knowledge of forensic dermatology to identify lesions from torture. OBJECTIVE: Review forensic dermatology in cases of torture. RESULTS: In provision of medical assessment and care to refugees and migrants, chronic skin lesions will be the most readily identifiable signs of torture. Beatings are common, with blunt force trauma resulting in postinflammatory hyperpigmentation. Torture burns can be thermal, chemical, or electrothermal, causing distinct lesions determined by the method, duration, and intensity of exposure, and area of skin affected. Sharp instruments inflict a wide range of lesions arising from stabbing/perforation or cuts from knives. Wound healing without medical attention and in unsanitary conditions will affect the scarring process. Lesions from suspension and ligatures may occur alongside scars from other forms of torture. Differential diagnoses include self-inflicted wounds, ethnic scarification, and scars from traditional healing practices. CONCLUSION: Physicians who may encounter survivors of torture in community or specialist practice would benefit from basic training in forensic dermatology, whereas knowledge of common forms of torture and cultural practices in refugees' countries of origin is important when considering differential diagnoses of skin lesions.

Diagnosis of congenital infections in premature, low-birthweight newborns with intrauterine growth restriction caused by cytomegalovirus (CMV), herpes simplex virus (HSV), Parvo-B 19, and Zika virus: a systematic review.

OBJECTIVES: To identify the prevalence of viral congenital infections in newborns classified as premature, low-birthweight, small for gestational age or intrauterine growth restriction. METHODS: The definition considered for selecting papers were: P as newborns younger than 28 days; V as low-birthweight, prematurity and intrauterine growth restriction; O as frequency of congenital infections with Cytomegalovirus, Parvovirus B19, Herpes Simplex, and Zika virus. The research was performed using EMBASE, LILACS, SCOPUS and MEDLINE databases, with no limitations on date and language. RESULTS: Eight studies were included. Manuscripts including Herpes Simplex, Zika virus or Parvovirus B19 did not fulfill the defined criteria. A wide variation in the frequency of CMV congenital infection (0-4.8%) was found, which might be attributed to regional and methodological differences between investigations. CONCLUSIONS: Newborn characteristics associated with CMV congenital infections may direct investigations towards these patients with a higher probability of infection. However, as data are controversial, studies concerning screening of infection are important to define recommendations of diagnosis.

Blood component utilization in COVID-19 patients in New York City: Transfusions do not follow the curve.

BACKGROUND: Blood suppliers and transfusion services have worked diligently to maintain an adequate blood supply during the COVID-19 pandemic. Our experience has shown that some COVID-19 inpatients require transfusion support; understanding this need is critical to blood product inventory management. STUDY DESIGN AND METHODS: Hospital-wide and COVID-19 specific inpatient blood product utilization data were collected retrospectively for our network's two tertiary academic medical centers over a 9-week period (March 1, 2020-May 2, 2020), when most inpatients had COVID-19. Utilization data were merged with a COVID-19 patient database to investigate clinical demographic characteristics of transfused COVID-19 inpatients relative to non-transfused ones. RESULTS: Overall, 11 041 COVID-19 patients were admitted and 364 received blood product transfusions for an overall transfusion rate of 3.3%. COVID-19 patients received 1746 blood components in total, the majority of which were red blood cells. COVID-19 patients' weekly transfusion rate increased as the pandemic progressed, possibly reflecting their increased severity of illness. Transfusion was significantly associated with several indicators of severe disease, including mortality, intubation, thrombosis, longer hospital admission, lower hemoglobin and platelet nadirs, and longer prothrombin and activated partial thromboplastin times. As the pandemic progressed, institutional adherence to transfusion guidelines improved for RBC transfusions compared to prior year trends but did not improve for platelets or plasma. CONCLUSION: There is a need to closely monitor the blood product inventory and demand throughout the COVID-19 pandemic as patients' transfusion needs may increase over time. Daily or weekly trending of patients' clinical status and laboratory values may assist blood banks in inventory management.

Pathology in Practice.

In collaboration with the American College of Veterinary Pathologists.

Exploring the association of intratumoral immune cell infiltrates with histopathologic grade in canine mast cell tumors.

Cutaneous canine mast cell tumors (ccMCTs) vary in their biological behavior, treatment, and prognosis, based on their grade. Immune cell infiltration has been associated with prognosis and response to treatments in some human cancers, and immune-targeting therapeutics are increasingly being explored in veterinary oncology. However, currently little is known about the tumor microenvironment (TME) in ccMCTs. Therefore, the objective of this study was to determine the prevalence of T lymphocytes, T regulatory lymphocytes, PD-1+ cells and macrophages in low- and high-grade ccMCTs. Thirty low-grade and 20 high-grade formalin-fixed paraffin-embedded ccMCT samples were included. Immunohistochemistry (IHC) was performed to detect CD3, FOXP3, Iba1, and PD-1 on sequential sections. Three 400x fields with the highest numbers of CD3+ cells were identified for each tumor. The percentage of CD3+, FOXP3+, and Iba1+ cells, and the number of PD-1+ cells, was quantified in each of these three "hot-spot" fields using ImageJ software. Iba1 expression was significantly greater in high-grade compared to low-grade ccMCTs (mean = 12.5% vs. 9.6%, p = 0.043). PD-1 expression was low overall, but a significantly higher number of PD-1-expressing cells was observed in high-grade ccMCTs (median 1 vs. 0, p = 0.001). No significant difference was noted in CD3 and FOXP3 expression between ccMCT grades. Macrophages and PD-1+ cells were more frequent in high-grade, compared to low-grade ccMCTs. Further studies are needed to define the role of macrophages and rare PD-1+ cells in high-grade ccMCTs.

Canine memory T-cell subsets in health and disease.

A more complete understanding of canine T-lymphocyte immunity is necessary for improving diagnostic and therapeutic approaches to canine diseases, developing cell-based canine immunotherapeutics, and evaluating dogs as large mammal models for comparative immunology research. The aim of this study was to utilize CD45RA (indicating antigen inexperience) and CD62L (indicating lymph node homing capability), to quantify canine memory T-cell subsets in healthy dogs and dogs with various diseases. Peripheral blood mononuclear cells (PBMCs) were prospectively collected from dogs belonging to one of four groups:dermatologic inflammation (n = 9), solid tumors (n = 9), lymphoma (n = 9), and age-/weight-matched healthy control dogs (n = 15). Dogs receiving prednisone or any other immunomodulating medication within two weeks were excluded. Flow cytometry was performed and T-cell subsets were defined as CD4+ or CD8+, and naïve (TN), central memory (CM), effector memory (EM), or terminal effector memory re-expressing CD45RA (TEMRA). T-cell subset proportions were compared between each disease group and their healthy age-/weight-matched controls using a Mann-Whitney test. Significantly increased %CD8+ TN (P = 0.036) and decreased %CD8+ TEMRA (P = 0.045) were detected in dogs with dermatologic inflammation compared to healthy controls. Furthermore, %CD4+ TN positively correlated with Canine Atopic Dermatitis Extent and Severity Index (CADESI) score within the inflammation group (ρ = 0.817, P = 0.011). No significant differences between either cancer group and their healthy controls were detected. Taken together, these data indicate that dermatologic inflammation can alter proportions of peripheral blood T-cell subsets, possibly due to the migration of antigen-specific T-cells into tissues. Furthermore, these findings support the utility of CD45RA and CD62L in characterizing clinical canine immune responses.

An Interesting Case of Isolated False-Reactive Hepatitis B Surface Antigen.

The standard serologic markers used to diagnose hepatitis B infection include hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), total hepatitis B core antibody (anti-HBc), and IgM antibody to hepatitis B core antigen (IgM anti-HBc). Different markers or combinations of markers are used to identify different phases of HBV infection and determine whether a patient has acute or chronic infection or immunity due to prior infection or vaccination or is seronegative and susceptible to future infection. Isolated HBsAg seropositivity is a peculiar serological pattern that requires investigation. Herein, we present a case of an asymptomatic female without a history of liver disease or evident risk factors for hepatitis, who underwent screening for infectious disease prior to resection of basal cell carcinoma involving her eyelid. The patient's laboratory testing showed positivity for HBsAg and the HIV 1/2 screen. To investigate, we performed serial dilutions, utilized heterophilicantibody blocking tubes, and repeated analysis using a different commercial assay (Abbott Architect i2000), all in support of a false-positive result attributed to a heterophilic antibody. Hence, we demonstrate that heterophilic antibody interference can result in isolated HBsAg positivity and recommend considering this form of interference in the differential where there is low clinical suspicion for viral infection.

Association of Age With SARS-CoV-2 Antibody Response.

Importance: Accumulating evidence suggests that children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more likely to manifest mild symptoms and are at a lower risk of developing severe respiratory disease compared with adults. It remains unknown how the immune response in children differs from that of adolescents and adults. Objective: To investigate the association of age with the quantity and quality of SARS-CoV-2 antibody responses. Design, Setting, and Participants: This cross-sectional study used 31 426 SARS-CoV-2 antibody test results from pediatric and adult patients. Data were collected from a New York City hospital from April 9 to August 31, 2020. The semiquantitative immunoglobin (Ig) G levels were compared between 85 pediatric and 3648 adult patients. Further analysis of SARS-CoV-2 antibody profiles was performed on sera from 126 patients aged 1 to 24 years. Main Outcomes and Measures: SARS-CoV-2 antibody positivity rates and IgG levels were evaluated in patients from a wide range of age groups (1-102 years). SARS-CoV-2 IgG level, total antibody (TAb) level, surrogate neutralizing antibody (SNAb) activity, and antibody binding avidity were compared between children (aged 1-10 years), adolescents (aged 11-18 years), and young adults (aged 19-24 years). Results: Among 31 426 antibody test results (19 797 [63.0%] female patients), with 1194 pediatric patients (mean [SD] age, 11.0 [5.3] years) and 30 232 adult patients (mean [SD] age, 49.2 [17.1] years), the seroprevalence in the pediatric (197 [16.5%; 95% CI, 14.4%-18.7%]) and adult (5630 [18.6%; 95% CI, 18.2%-19.1%]) patient populations was similar. The SARS-CoV-2 IgG level showed a negative correlation with age in the pediatric population (r = -0.45, P < .001) and a moderate but positive correlation with age in adults (r = 0.24, P < .001). Patients aged 19 to 30 years exhibited the lowest IgG levels (eg, aged 25-30 years vs 1-10 years: 99 [44-180] relative fluorescence units [RFU] vs 443 [188-851] RFU). In the subset cohort aged 1 to 24 years, IgG, TAb, SNAb and avidity were negatively correlated with age (eg, IgG: r = -0.51; P < .001). Children exhibited higher median (IQR) IgG levels, TAb levels, and SNAb activity compared with adolescents (eg, IgG levels: 473 [233-656] RFU vs 191 [82-349] RFU; P < .001) and young adults (eg, IgG levels: 473 [233-656] RFU vs 85 [38-150] RFU; P < .001). Adolescents also exhibited higher median (IQR) TAb levels, IgG levels, and SNAb activity than young adults (eg, TAb levels: 961 [290-2074] RFU vs 370 [125-697]; P = .006). In addition, children had higher antibody binding avidity compared with young adults, but the difference was not significant. Conclusions and Relevance: The results of this study suggest that SARS-CoV-2 viral specific antibody response profiles are distinct in different age groups. Age-targeted strategies for disease screening and management as well as vaccine development may be warranted.

Acinetobacter radioresistens infection with bacteremia and pneumonia.

Acinetobacter species are non-fermentative Gram-negative coccobacilli that are ubiquitous in the environment. The archetype pathogen within the genus is Acinetobacter baumannii, however, other species have the potential to cause human infection, especially in the hospital setting. We describe a patient with infection due to Acinetobacter radioresistens, a rare agent of human disease, which is often misidentified using biochemical methods. Acinetobacter radioresistens is the source of the Class D OXA-23 carbapenemase that can confer carbapenem resistance in A. baumannii. Therefore, accurate identification of A. radioresistens is important for clinical management and to potentially prevent the spread of carbapenem resistance.

Influence of thickness and incisal extension of indirect veneers on the biomechanical behavior of maxillary canine teeth.

OBJECTIVES: To analyze the influence of thickness and incisal extension of indirect veneers on the stress and strain generated in maxillary canine teeth. MATERIALS AND METHODS: A 3-dimensional maxillary canine model was validated with an in vitro strain gauge and exported to computer-assisted engineering software. Materials were considered homogeneous, isotropic, and elastic. Each canine tooth was then subjected to a 0.3 and 0.8 mm reduction on the facial surface, in preparations with and without incisal covering, and restored with a lithium disilicate veneer. A 50 N load was applied at 45° to the long axis of the tooth, on the incisal third of the palatal surface of the crown. RESULTS: The results showed a mean of 218.16 µstrain of stress in the in vitro experiment, and 210.63 µstrain in finite element analysis (FEA). The stress concentration on prepared teeth was higher at the palatal root surface, with a mean value of 11.02 MPa and varying less than 3% between the preparation designs. The veneers concentrated higher stresses at the incisal third of the facial surface, with a mean of 3.88 MPa and a 40% increase in less-thick veneers. The incisal cover generated a new stress concentration area, with values over 48.18 MPa. CONCLUSIONS: The mathematical model for a maxillary canine tooth was validated using FEA. The thickness (0.3 or 0.8 mm) and the incisal covering showed no difference for the tooth structure. However, the incisal covering was harmful for the veneer, of which the greatest thickness was beneficial.

Social Impact of Facial Infantile Hemangiomas in Preteen Children.

IMPORTANCE: Involuted infantile facial hemangiomas (IHs) may adversely affect the social skills of children. OBJECTIVE: To assess the social impact of involuted facial IHs, with or without prior treatment, in preteen children. DESIGN, SETTING, AND PARTICIPANTS: An observational, cross-sectional study of social anxiety and skills in preteen children with facial IHs diagnosed during infancy. The study took place in an academic institution and a community dermatology practice between January 1, 2013, and July 30, 2014. Records on 236 children with IHs located in a cosmetically sensitive area were identified; of those, 144 potential participants (parents) were reached by telephone and mailed study packets. Thirty completed questionnaires were returned. Data analysis was performed from August 1, 2014, to September 7, 2015. INTERVENTIONS: The questionnaires included the following psychiatric scales: (1) Social Anxiety Scale for Children-Revised (SASC-R), completed by parents and children, including the domains of Fear of Negative Evaluation and Social Avoidance/Distress in New Situations (SAD-New) (higher scores indicate greater social anxiety), and (2) Social Competency Inventory (SCI), completed by parents, including the domains of Prosocial Behavior and Social Initiative (lower scores indicate poorer social competency). MAIN OUTCOMES AND MEASURES: Demographics, clinical details, and survey responses were collected. Analysis was conducted using t tests to compare scores for each survey domain with established normative data and between sex as well as between treatment vs nontreatment groups. RESULTS: Of the 144 potential participants, 30 (21%) responded. The mean age of the preteen subjects was 10.0 years (range, 5.4-12.9 years) with a 2:1 female to male ratio. Twenty-five children (83%) had a single IH, and the remaining 5 participants (17%) had multiple IHs, with at least 1 IH in a cosmetically sensitive area. The periocular region was the most common site of the IH (10 [33%]), followed by the nose (6 [20%]), cheek (5 [17%]), forehead (4 [13%]), lip or perioral region (4 [13%]), and ear (1 [3%]). Eighteen children (60%) had received treatment for their IH. With results reported as mean (SD), the SASC-R test showed that social anxiety of the children was not increased over normative data; however, those who did not receive IH treatment had significantly greater anxiety for new situations compared with those who received treatment (SAD-New: 15.5 [5.1] vs 11.5 [3.8]; P = .02). Results of the SCI scale indicated that the Prosocial Orientation domain score for the children was similar to normative data (3.96 [0.48] vs 3.89 [0.55], P = .50). Social Initiative domain scores were significantly poorer in children who did not receive treatment vs those who received treatment (3.45 [0.43] vs 4.03 [0.55]; P = .006). CONCLUSIONS AND RELEVANCE: Preteen children with involuted, untreated facial IHs have higher Social Anxiety domain scores in new situations and decreased Social Initiative domain scores compared with children who receive treatment for facial IH. Although this study is limited by a small sample size, it raises important considerations for whether early treatment of facial IHs in cosmetically sensitive areas has a beneficial effect on social skills in preteens.

Percepção dos profissionais de saúde sobre a atuação de acadêmicos no contexto da Atenção Primária / Perception of health professionals on undergraduate students acting in the context of primary care

A Atenção Primária em Saúde (APS) é um cenário importante para a graduação dos cursos na área da saúde. Objetiva-se descrever e analisar a percepção dos profissionais da saúde de uma Unidade Básica de Saúde (UBS) sobre a atuação dos acadêmicos de enfermagem, medicina e odontologia. Trata-se de um estudo descritivo e exploratório de abordagem qualitativa, por meio da realização de entrevistas semiestruturadas aplicadas a profissionais atuantes na UBS em questão. A UBS apresentou recursos humanos adequados para atender às necessidades dos estudantes, mas uma insuficiência na estrutura física. A atuação dos estudantes traz contribuições para a organização do serviço e atendimento da população, apesar de diminuir a agilidade do serviço e limitar a longitudinalidade nos atendimentos. Conclui-se que a participação de estudantes na UBS agrega valor e é necessária para a formação acadêmica, como meio de ampliar a compreensão do processo saúde-doença e das possibilidades de cuidado.

Primary Health Care (PHC) is an important scenario for undergraduate health courses. The objective is to describe and analyse the perception of health professionals on undergraduate students on nursing, medicine, and dentistry acting in a Basic Health Unit (BHU). It is a descriptive and exploratory study of a qualitative approach with personal semi-structured interviews applied to professionals working in the BHU. The unit presents adequate human resources to attend to the students' needs, despite the physical structure being unsatisfying. The undergraduate students' performance brings contributions to the organization of the service and attendance of the population, although it can reduce and limit the agility and the longitudinality of the service. Through this study, the undergraduate students' participation in the BHU adds value and is essential for academic training as a means to broaden the understanding of the health-disease process and the treatment possibilities.

Influence of the occlusal contacts in formation of Abfraction Lesions in the upper premolar / Influência dos contatos oclusais na formação de lesões de Abfração no pré-molar superior

Objective: The aim of this study was to observe the influence of different occlusal contacts in a superior pre-molar structure using Finite Element Analysis. Material and Methods: A three-dimensional model of a superior pre-molar was designed to simulate three occlusion situations, namely central occlusion and two types of lateral occlusion contacts. The model presents enamel, dentin, a periodontal ligament and a fixation cylinder separately. All materials were considered isotropic, linear and homogeneous, and the contacts of each structure were perfectly bonded. On analysis software, a load was applied to an occlusal surface at 40° to the long axis on lateral contacts, and directed to the long axis on central occlusion contact. Results: The results were obtained in stress maps and the maximum values were then plotted in table for quantitative comparison, with the enamel concentrating more stress than dentin and the occlusal contact presenting the worst biomechanical behavior. Conclusion: Within the limitations of this study, it is possible conclude that: eccentric contacts have higher potential to develop abfraction lesions on the cervical region of teeth, thus increasing the magnitude of tensile and shear stresses. (AU)

Objetivo: observar a influência de diferentes contatos oclusais em uma estrutura pré-molar superior usando a análise por elementos finitos. Material e Métodos: um modelo tridimensional de pré-molar superior foi projetado para simular três situações de oclusão: oclusão central e dois tipos de contatos de oclusão lateral. O modelo apresentou esmalte, dentina, ligamento periodontal e um cilindro de fixação separadamente. Todos os materiais foram considerados isotrópicos, lineares e homogêneos, e os contatos de cada estrutura foram considerados perfeitamente ligados. No software de análise, aplicou-se uma carga na superfície oclusal a 40°, ao longo eixo do dente, nos contatos laterais e direcionada para apical no contato de oclusão central. Resultados: os resultados foram obtidos nos mapas de tensão e os valores máximos foram escritos em tabela para comparação quantitativa, com o esmalte concentrando mais tensão do que a dentina e o contato em cúspide de balanceio apresentando o pior comportamento biomecânico. Conclusão: dentro das limitações deste estudo, é possível concluir que: os contatos excêntricos facilitam o surgimento de lesões de abfração na região cervical dos dentes, pois aumentam a magnitude das tensões de tração e de cisalhamento. (AU)