Thousands of induced germline mutations affecting immune cells identified by automated meiotic mapping coupled with machine learning.

Forward genetic studies use meiotic mapping to adduce evidence that a particular mutation, normally induced by a germline mutagen, is causative of a particular phenotype. Particularly in small pedigrees, cosegregation of multiple mutations, occasional unawareness of mutations, and paucity of homozygotes may lead to erroneous declarations of cause and effect. We sought to improve the identification of mutations causing immune phenotypes in mice by creating Candidate Explorer (CE), a machine-learning software program that integrates 67 features of genetic mapping data into a single numeric score, mathematically convertible to the probability of verification of any putative mutation-phenotype association. At this time, CE has evaluated putative mutation-phenotype associations arising from screening damaging mutations in ∼55% of mouse genes for effects on flow cytometry measurements of immune cells in the blood. CE has therefore identified more than half of genes within which mutations can be causative of flow cytometric phenovariation in Mus musculus The majority of these genes were not previously known to support immune function or homeostasis. Mouse geneticists will find CE data informative in identifying causative mutations within quantitative trait loci, while clinical geneticists may use CE to help connect causative variants with rare heritable diseases of immunity, even in the absence of linkage information. CE displays integrated mutation, phenotype, and linkage data, and is freely available for query online.

Comparison of the effect of cigarette smoke on mesenchymal stem cells and dental stem cells.

The persistent prevalence of cigarette smoking continues to contribute to preventable disease and death in the United States. Although much is known about the deleterious systemic effects of cigarette smoke and nicotine, some clinically relevant areas, such as the impact of cigarette smoke and nicotine on stem cells and the subsequent implications in regenerative medicine, still remain unclear. This review focuses on recent studies on the effect of cigarette smoke and one of its deleterious components, nicotine, on mesenchymal stem cells, with an emphasis on dental stem cells.

Antimalarial activity of 2,6-dibenzylidenecyclohexanone derivatives.

Malaria remains one of the deadliest infectious diseases worldwide and continues to infect hundreds of millions of individuals each year. Here we report the discovery and derivatization of a series of 2,6-dibenzylidenecyclohexanones targeting the chloroquine-sensitive 3D7 strain of Plasmodium falciparum . While the initial lead compound displayed significant toxicity in a human cell proliferation assay, we were able to identify a derivative with no detectable toxicity and sub-micromolar potency.

Septic Arthritis of the Temporomandibular Joint: A Systematic Review.

PURPOSE: The purpose of this study was to describe the characteristics of the patient history, clinical findings, laboratory tests, treatment, and long-term function of septic arthritis of the temporomandibular joint (SATMJ). METHODS: All articles in the English literature related to SATMJ were queried using PubMed, Embase, and the Cochrane Library (1950 to July 1, 2020). The reference lists were reviewed for additional articles. RESULTS: A preliminary search of the literature returned 241 results, of which 37 met inclusion criteria, with an additional article from reference review. There were 93 total cases, with a mean age of 35.7 years (0.1 to 85). Symptoms mostly consisted of pain in the temporomandibular joint/preauricular region (n = 84, 90.3%), trismus (n = 73, 78.5%), and facial/preauricular swelling (n = 68, 73.1%). Most patients had no systemic symptoms (n = 80, 86.1%). The mean degree of mouth opening was 13.1 mm (5 to 35). Diagnosis was made with the following imaging modalities: radiograph (n = 48, 51.6%), CT scan (n = 35, 37.6%), MRI (n = 25, 26.9%), and ultrasound (n = 3, 3.2%). Staphylococcus aureus (n = 19, 20.4%) was most commonly isolated. About 92 patients (98.9%) received antibiotics and 85 patients underwent surgery (eg, arthrocentesis, arthroscopy, etc.), of which 15 patients (17.6%) required repeat surgery. Most long-term outcomes were favorable. Sequelae occurred in 26 of 85 patients (30.6%) with documented follow-up. CONCLUSIONS: SATMJ should be suspected in the presence of trismus, jaw pain, and preauricular swelling. Management includes prompt evaluation and treatment with broad-spectrum antibiotics. Surgery is not always indicated but can be life-saving in severe cases.

Simplified White Blood Cell Differential: An Inexpensive, Smartphone- and Paper-Based Blood Cell Count.

Sorting and measuring blood by cell type is extremely valuable clinically and provides physicians with key information for diagnosing many different disease states including: leukemia, autoimmune disorders, bacterial infections, etc. Despite the value, the present methods are unnecessarily costly and inhibitive particularly in resource poor settings, as they require multiple steps of reagent and/or dye additions and subsequent rinsing followed by manual counting using a hemocytometer, or they require a bulky, expensive equipment such as a flow cytometer. While direct on-paper imaging has been considered challenging, paper substrate offers a strong potential to simplify such reagent/dye addition and rinsing. In this work, three-layer paper-based device is developed to automate such reagent/dye addition and rinsing via capillary action, as well as separating white blood cells (WBCs) from whole blood samples. Direct onpaper imaging is demonstrated using a commercial microscope attachment to a smartphone coupled with a blue LED and 500 nm long pass optical filter. Image analysis is accomplished using an original MATLAB code, to evaluate the total WBC count, as well as differential WBC count, i.e., granulocytes (primarily neutrophils) vs. agranulocytes (primarily lymphocytes). Only a finger-prick of whole blood is required for this assay. The total assay time from finger-prick to data collection is under five minutes. Comparison with a hemocytometry-based manual counting corroborates the accuracy and effectiveness of the proposed method. This approach could be potentially used to help make blood cell counting technologies more readily available, especially in resource poor, point-of-care settings.

Association between traditional clinical high-risk features and gene expression profile classification in uveal melanoma.

PURPOSE: To evaluate the association between traditional clinical high-risk features of uveal melanoma patients and gene expression profile (GEP). METHODS: This was a retrospective, single-center, case series of patients with uveal melanoma. Eighty-three patients met inclusion criteria for the study. Patients were examined for the following clinical risk factors: drusen/retinal pigment epithelium (RPE) changes, vascularity on B-scan, internal reflectivity on A-scan, subretinal fluid (SRF), orange pigment, apical tumor height/thickness, and largest basal dimensions (LBD). A novel point system was created to grade the high-risk clinical features of each tumor. Further analyses were performed to assess the degree of association between GEP and each individual risk factor, total clinical risk score, vascularity, internal reflectivity, American Joint Committee on Cancer (AJCC) tumor stage classification, apical tumor height/thickness, and LBD. RESULTS: Of the 83 total patients, 41 were classified as GEP class 1A, 17 as class 1B, and 25 as class 2. The presence of orange pigment, SRF, low internal reflectivity and vascularity on ultrasound, and apical tumor height/thickness ≥ 2 mm were not statistically significantly associated with GEP class. Lack of drusen/RPE changes demonstrated a trend toward statistical association with GEP class 2 compared to class 1A/1B. LBD and advancing AJCC stage was statistically associated with higher GEP class. CONCLUSIONS: In this cohort, AJCC stage classification and LBD were the only clinical features statistically associated with GEP class. Clinicians should use caution when inferring the growth potential of melanocytic lesions solely from traditional funduscopic and ultrasonographic risk factors without GEP data.

Prognostic significance of corticotroph staining in radiosurgery for non-functioning pituitary adenomas: a multicenter study.

Silent corticotroph staining pituitary adenoma (SCA) represents an uncommon subset of Non-Functioning adenomas (NFAs), hypothesized to be more locally aggressive. In this retrospective multicenter study, we investigate the safety and effectiveness of Stereotactic Radiosurgery (SRS) in patients with SCA compared with other non-SCA NFA's. Eight centers participating in the International Gamma-Knife Research Foundation (IGKRF) contributed to this study. Outcomes of 50 patients with confirmed SCAs and 307 patients with confirmed non-SCA NFA's treated with SRS were evaluated. Groups were matched. SCA was characterized by a lack of clinical evidence of Cushing disease, yet with positive immunostaining for corticotroph. Median age was 55.2 years (13.7-87). All patients underwent at least one trans-sphenoidal tumor resection prior to SRS. SRS parameters were comparable as well. Median follow-up 40 months (6-163). Overall tumor control rate (TCR) 91.2% (n = 280). In the SCA group, TCR were 82% (n = 41) versus 94.1% (n = 289) for the control-NFA (p = 0.0065). The SCA group showed a significantly higher incidence of new post-SRS visual deficit (p < 0.0001) assigned to tumor progression and growth, and post-SRS weakness and fatigue (p < 0.0001). In univariate and multivariate analysis, only the status of silent corticotroph staining (p = 0.005, p = 0.009 respectively) and margin dose (p < 0.0005, p = 0.0037 respectively) significantly influenced progression rate. A margin dose of ≥17 Gy was noted to influence the adenoma progression rate in the entire cohort (p = 0.003). Silent corticotroph staining represents an independent factor for adenoma progression and hypopituitarism after SRS. A higher margin dose may convey a greater chance of TCR.

Transiliac-Shortening Osteotomy to Treat Ischial Pressure Injury due to Fixed Pelvic Obliquity: A Case Report.

CASE: A 17-year-old adolescent boy with Gross Motor Function Classification System 5 cerebral palsy and neuromuscular scoliosis underwent posterior spinal fusion and segmental spinal instrumentation from T3 to the pelvis. He developed a right ischial pressure injury a few months postoperatively, which persisted despite nonoperative measures. He subsequently underwent an ipsilateral transiliac-shortening osteotomy 16 months after spinal surgery to treat his residual pelvic obliquity and the ischial pressure injury, which healed completely. At the 1-year follow-up visit, there were no further signs of pressure injury. CONCLUSION: This case report describes transiliac-shortening osteotomy as a viable treatment option for non-healing ischial pressure injuries secondary to fixed pelvic obliquity.

Flow diversion for basilar quadrifurcation aneurysms.

BACKGROUND: Flow-diverting devices (FDDs), such as the Pipeline Embolization Device, have been gaining traction for treating challenging posterior circulation aneurysms. Few previous studies have focused on using FDDs to treat aneurysms of the basilar quadrifurcation. METHODS: We retrospectively reviewed the use of FDDs to treat patients with basilar quadrifurcation aneurysms. Patients were assessed for aneurysm type, previous aneurysm treatment, technical success, periprocedural complications, and long-term aneurysm occlusion. RESULTS: 34 patients were assessed; aneurysms of the basilar apex (n=23) or superior cerebellar artery (SCA) (n=7), or both (n=1), and posterior cerebral artery (PCA) (n=3). The mean (SD) largest aneurysm dimension was 8.7 (6.1) mm (range 1.9-30.8 mm). 14 aneurysms were previously surgically clipped or endovascularly coiled. All aneurysms had a saccular morphology. Complete or near-complete occlusion was achieved in 30 of 34 patients (88%) at final angiographic follow-up, a mean (SD) of 6.6 (5.4) months (range 0-19 months) postoperatively. No patient experienced postoperative symptomatic occlusions of the SCA or PCA; 4 patients developed asymptomatic posterior communicating artery occlusions; 28 patients (82%) experienced no complications; whereas 3 (9%) experienced major complications and 3 (9%) experienced minor complications; and 1 patient died as a result of subarachnoid hemorrhage. CONCLUSION: Flow diversion may be a safe and effective option to treat basilar quadrifurcation aneurysms. Previously treated basilar quadrifurcation aneurysms with recurrence or residual lesion may benefit from additional treatment with an FDD. Further prospective studies should be directed toward validating these findings.

The association of thromboembolic complications and the use of tranexamic acid during resection of intracranial meningiomas: systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Antifibrinolytics, such as tranexamic acid (TXA), have been shown to decrease intraoperative blood loss across multiple surgical disciplines. However, they carry the theoretical risk of thromboembolic events secondary to induced hypercoagulability. Therefore, the aim of this study was to systematically review the available literature and perform a meta-analysis on the use of TXA in meningioma resection to assess thromboembolic risks. METHODS: The PubMed, Web of Science, and Google Scholar databases were reviewed for all randomized controlled trials presenting primary data on TXA use during resection of intracranial meningiomas. Data were gathered on operative duration, venous thromboembolic complications, deep venous thrombosis, use of allogeneic blood transfusion, estimated blood loss (EBL), and postoperative hemoglobin. Patients who received TXA were compared with controls who did not receive TXA intraoperatively using random-effects models. RESULTS: A total of 508 unique articles were identified, of which 493 underwent full-text review. Ultimately, 6 studies with 381 total patients (190 receiving TXA) were included in the final analysis. All 6 trials were randomized, blinded, and placebo controlled with a TXA administration rate of a 20-mg/kg load followed by a 1-mg/kg/hr infusion. All studies were performed in lower-middle-income countries. There were no reported instances of venous thromboembolism (VTE) in the TXA and non-TXA cohorts. Patients receiving TXA exhibited fewer allogeneic transfusions (21.5% vs 41.6% [OR 0.26, 95% CI 0.09-0.77], p = 0.02) and lower EBL (MD -282.48 mL [95% CI -367.77 to -197.20 mL], p < 0.001) compared with patients who did not receive TXA, and they also had lower rates of perioperative complications (10.7% vs 19.9% [OR 0.47, 95% CI 0.2-0.95], p = 0.04). CONCLUSIONS: Current literature suggests that TXA is not associated with increased risk for VTE when administered during resection of intracranial meningioma. TXA appears to decrease intraoperative blood loss and allogeneic transfusion requirements during meningioma resection and thus may improve the safety of surgical management of this pathology.

Alfred Washington Adson: Perspectives on Intracranial Neurosurgery and the Responsibilities of the Neurosurgeon.

In a period when the budding field of neurosurgery was believed to have little promise, Dr Alfred Washington Adson founded and led the first neurosurgical department at Mayo Clinic. He was not without reservations-surgical intervention for neurological conditions was rarely pursued because of poor outcomes and high complication rates, and Dr Adson acknowledged his early concerns about the future of neurosurgery in his memoirs. However, his education, mentorship, his training, and his first neurosurgical cases helped to shape the impact he ultimately had on the field and his legacy as a neurosurgeon. Dr Adson trained with several renowned Mayo general surgeons, notably his mentor Dr Emil Beckman, whose desire for operative precision shaped Dr Adson's drive to develop his own skills as a surgeon. Two years into his residency, he became the youngest staff surgeon and was tasked with managing the neurosurgical cases at Mayo. The five neurosurgical cases overseen by Dr Adson in the next year illuminated the opportunity for neurosurgery to drastically improve the lives of patients. Dr Adson, given the option of continuing as either a general surgeon or a neurosurgeon, ultimately chose to pursue neurosurgery. This article seeks to provide a historical perspective on the neurosurgeon Dr Alfred Washington Adson using primary and secondary accounts from the Mayo archives, highlighting his contributions to the early understanding of intracranial pathology and how his early experiences as a trainee developed into a personal passion for self-improvement, education, and advocacy for health care in America.

Resolution of brachioradial pruritus following anterior cervical discectomy and fusion: a case report.

Background: Brachioradial pruritus (BRP) is a rare, chronic condition that typically presents in middle-aged light-skinned females as itching of the dorsolateral upper extremities in the C5-C6 dermatome distribution. Cervical nerve compression and ultraviolet (UV) radiation are largely considered to be causative factors. There have been very few case reports where surgical decompression was used to treat BRP. This case report is unique because our patient had a brief period of symptom recurrence 2 months post-operation as supported by displacement of the cage on imaging. The patient then underwent implant removal and revision with the use of an anterior plate leading to complete symptom resolution. Case Description: A 72-year-old female presenting with a 2-year history of severe, persistent pruritus and mild pain of bilateral arms and forearms. The patient was being followed by her dermatologic providers for 10+ years for other unrelated diagnoses. She was referred to our office after having trialed multiple topical medications, oral medications, and injections without lasting definitive success. Cervical spine radiographs demonstrated severe degenerative disc disease with osteophyte formation at C5-C6. Cervical magnetic resonance imaging (MRI) revealed disc herniation at C5-C6 causing mild cord compression with bilateral foraminal stenosis. Patient proceeded with anterior cervical discectomy and fusion at C5-C6, which provided immediate symptom relief. Two months post-operation, her symptoms recurred and repeat cervical spine radiographs revealed cage migration. The patient underwent a revision of fusion by removal of the cage and placement of an anterior plate. At her most recent 2-year follow-up visit, she has been doing well post-operatively without any pain or pruritus. Conclusions: This case report illustrates the use of surgical intervention as a viable treatment option for specific patients with persistent BRP that have failed all other forms of conservative management. Cervical radiculopathy should be included in the differential diagnosis until ruled out by advanced imaging, particularly in cases of BRP that are refractory to standard dermatological treatment.

Telemedicine and Otolaryngology in the COVID-19 Era.

OBJECTIVE: The global Coronavirus disease 2019 (COVID-19) pandemic has resulted in an expansion of telemedicine. The purpose of this study is to present our experience with outpatient telemedicine visits within a single institution's Department of Otolaryngology during the initial COVID-19 era. STUDY DESIGN: Retrospective chart review. METHODS: This was a single-institution study conducted within the Department of Otolaryngology at an urban tertiary care center. Data on outpatient visits was obtained from billing and scheduling records from January 6 to May 28, 2020. Visits were divided into "pre-shutdown" and "post-shutdown" based on our state's March 23, 2020 COVID-19 shutdown date. RESULTS: A total of 3447 of 4340 (79.4%) scheduled visits were completed in the pre-shutdown period as compared to 1451 of 1713 (84.7%) in the post-shutdown period. The proportion of telemedicine visits increased (0.7%-81.2%, P < .001). Overall visit completion rate increased following the shutdown (80.2%-84.7%, P < .001). Subspecialties with an increase in visit completion rate were general (76.9%-88.0%, P = .002), otology (77.4%-87.2%, P < .001), and rhinology (80.0%-86.2%, P = .003). Patients with Medicaid and Medicare had higher appointment completion rates following the transition to telemedicine visits (80.7%-85.7%, P = .002; 76.9%-84.7%, P = .001). Older age was associated with decreased appointment cancellation pre-shutdown (OR 0.994 [0.991-0.997], P < .001) but increased appointment cancellation post-shutdown (OR 1.008 [1.001-1.014], P = .015). Mean COVID-19 risk scores were unchanged (P = .654). CONCLUSIONS: COVID-19 has led to major changes in outpatient practice, with a significant shift from in-person to telemedicine visits following the mandatory shutdown. An associated increase in appointment completion rates was observed, reflecting a promising viable alternative to meet patient needs during this unprecedented time.

Unilateral Cordotomy: A Systematic Review of Efficacy and Outcomes.

INTRODUCTION: Glottic obstruction may arise secondary to bilateral vocal fold immobility (BVFI). Treatment options include a tracheostomy to bypass the site of obstruction as well as unilateral transverse cordotomy to alleviate the obstruction. The objective of this review is to determine the efficacy, adverse event profile, and long-term outcomes, including the need for tracheostomy, in patients undergoing unilateral cordotomy. METHODS: The Preferred Reporting Systems for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed for this systematic review. A literature search of unilateral cordotomy was performed by searching PubMed, Cochrane Library, and Embase. Articles presenting cases of BVFI treated with unilateral cordotomy were included. Review articles, animal studies, non-English-language articles, and abstracts were excluded. Articles presenting cases of bilateral cordotomy or cordotomy with arytenoidectomy were excluded. RESULTS: We identified 14 studies and 291 patients undergoing unilateral cordotomy. Sixty-eight patients had a prior tracheostomy in place at the time of cordotomy. The most common post-operative complication was granulation tissue formation (n = 39). Thirty-one patients developed glottic edema with subsequent dyspnea. Three patients developed scarring of the primary cordotomy site with the return to an obstructed airway. Nine patients required a post-cordotomy tracheostomy due to these complications. Five patients required a long-term tracheostomy and were unable to be decannulated. CONCLUSION: Unilateral cordotomy is an effective treatment for glottic obstruction with high post-operative decannulation rates. Adverse events including worsening glottic obstruction are uncommon, although edema and granulation tissue may develop in the post-operative period and necessitate close post-operative monitoring. Laryngoscope, 133:6-14, 2023.

A portable immunosensor provides sensitive and rapid detection of Borrelia burgdorferi antigen in spiked blood.

There are no assays for detecting B. burgdorferi antigen in blood of infected Lyme disease individuals. Here, we provide proof-of-principle evidence that we can quantify B. burgdorferi antigen in spiked blood using a portable smartphone-based fluorescence microscope that measures immunoagglutination on a paper microfluidic chip. We targeted B. burgdorferi OspA to develop a working prototype and added examples of two antigens (OspC and VlsE) that have diagnostic value for discrimination of Lyme disease stage. Using an extensively validated monoclonal antibody to OspA (LA-2), detection of OspA antigen had a broad linear range up to 100 pg/mL in 1% blood and the limit of detection (LOD) was 100 fg/mL (= 10 pg/mL in undiluted blood), which was 1000 times lower than our target of 10 ng/mL. Analysis of the two other targets was done using polyclonal and monoclonal antibodies. OspC antigen was detected at LOD 100 pg/mL (= 10 ng/mL of undiluted blood) and VlsE antigen was detected at LOD 1-10 pg/mL (= 0.1-1 ng/mL of undiluted blood). The method is accurate and was performed in 20 min from sample to answer. When optimized for detecting several B. burgdorferi antigens, this assay may differentiate active from past infections and facilitate diagnosis of Lyme disease in the initial weeks of infection, when antibody presence is typically below the threshold to be detected by serologic methods.

Neutrophil to Lymphocyte Ratio as a Predictor of Postoperative Outcomes in Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

(1) Introduction: Traumatic brain injury (TBI) is a leading cause of injury and mortality worldwide, carrying an estimated cost of $38 billion in the United States alone. Neutrophil to lymphocyte ratio (NLR) has been investigated as a standardized biomarker that can be used to predict outcomes of TBI. The aim of this review was to determine the prognostic utility of NLR among patients admitted for TBI. (2) Methods: A literature search was conducted in PubMed, Scopus, and Web of Science in November 2022 to retrieve articles regarding the use of neutrophil to lymphocyte ratio (NLR) as a prognostic measure in traumatic brain injury (TBI) patients. Inclusion criteria included studies reporting outcomes of TBI patients with associated NLR values. Exclusion criteria were studies reporting only non-primary data, those insufficiently disaggregated to extract NLR data, and non-English or cadaveric studies. The Newcastle-Ottawa Scale was utilized to assess for the presence of bias in included studies. (3) Results: Following the final study selection 19 articles were included for quantitative and qualitative analysis. The average age was 46.25 years. Of the 7750 patients, 73% were male. Average GCS at presentation was 10.51. There was no significant difference in the NLR between surgical vs. non-surgical cohorts (SMD 2.41 95% CI -1.82 to 6.63, p = 0.264). There was no significant difference in the NLR between bleeding vs. non-bleeding cohorts (SMD 4.84 95% CI -0.26 to 9.93, p = 0.0627). There was a significant increase in the NLR between favorable vs. non-favorable cohorts (SMD 1.31 95% CI 0.33 to 2.29, p = 0.0090). (4) Conclusions: Our study found that NLR was only significantly predictive for adverse outcomes in TBI patients and not surgical treatment or intracranial hemorrhage, making it nonetheless an affordable alternative for physicians to assess patient prognosis.

Gaps in Prenatal Hepatitis B Screening and Management of HBsAg Positive Pregnant Persons in the U.S., 2015-2020.

BACKGROUND: The Advisory Committee for Immunization Practices (ACIP) recommends testing all pregnant women for hepatitis B surface antigen (HBsAg) and testing HBsAg-positive pregnant women for hepatitis B virus deoxyribonucleic acid (HBV DNA). HBsAg-positive pregnant persons are recommended by the American Association for the Study of Liver Diseases to receive regular monitoring, including alanine transaminase (ALT) and HBV DNA and antiviral therapy for active hepatitis and to prevent perinatal HBV transmission if HBV DNA level is >200,000 IU/mL. METHODS: Using Optum Clinformatics Data Mart Database claims data, pregnant women who received HBsAg testing and HBsAg-positive pregnant persons who received HBV DNA and alt testing and antiviral therapy during pregnancy and after delivery during January 1, 2015-December 31, 2020 were analyzed. RESULTS: Among 506,794 pregnancies, 14.6% did not receive HBsAg testing. Pregnant women more likely to receive testing for HBsAg (p<0.01) were persons aged ≥20 years, were Asian, had >1 child, or received education beyond high school. Among the 0.28% (1,437) pregnant women who tested positive for hepatitis B surface antigen, 46% were Asian. The proportion of HBsAg-positive pregnant women who received HBV DNA testing during pregnancy and in the 12 months after delivery was 44.3% and 28.6%, respectively; the proportion that received hepatitis B e antigen was 31.6% and 12.7%, respectively; the proportion that received ALT testing was 67.4% and 47%, respectively; and the proportion that received HBV antiviral therapy was 7% and 6.2%, respectively. CONCLUSIONS: This study suggests that as many as half a million (∼14%) pregnant persons who gave birth each year were not tested for HBsAg to prevent perinatal transmission. More than 50% of HBsAg-positive persons did not receive the recommended HBV-directed monitoring tests during pregnancy and after delivery.

Brief Report: High Levels of CD47 Expression in Thymic Epithelial Tumors.

Introduction: CD47 is a tumor antigen that inhibits phagocytosis leading to immune evasion. Anti-CD47 therapy is a promising new immunotherapy across numerous tumor types, but it has not been tested in thymic epithelial tumors (TETs): thymomas and thymic carcinomas. TETs are rare tumors that are difficult to treat, especially with programmed cell death protein 1/programmed death-ligand 1 checkpoint inhibitors, owing to the excessive rates of immune-related adverse events. This study investigated the levels of CD47 expression in TETs to explore the possibility of anti-CD47 therapy. Methods: A total of 67 thymic tumors (63 thymomas and 4 thymic carcinomas) and 14 benign thymus controls and their clinical data were included. Samples were stained for CD47 expression (rabbit monoclonal antibody SP279, Abcam, Waltham, MA) and scored for both intensity and H-score (intensity multiplied by the percentage of tumor involved). Intensity was defined as follows: 0 = none, 1 = weak, 2 = moderate, and 3 = strong. H-scores ranged from 0 to 300. Samples with an intensity score below 2 or an H-score below 150 were considered CD47low, whereas the rest were CD47high. Results: Compared with normal thymic tissues, TETs were more frequently CD47 positive and had significantly higher levels of CD47 expression. CD47 was positive in 79.1% of TETs compared with 57.1% of normal thymus. The level of CD47 expression was 16-fold higher in TETs (mean H-score 75.0 versus 4.6, p = 0.003). Multivariate analysis adjusted for age, sex, stage, resection status, and performance status revealed that CD47-high tumors were highly correlated with WHO histology type (p = 0.028). The most frequent CD47high tumors, in contrast to CD47low tumors, were types A (28.6% versus 7.5%) and AB (57.1% versus 13.2%), and the least frequent were B1 (7.1% versus 24.5%), B2 (0% versus 35.8%), B3 (7.1% versus 11.3%), and C (0% versus 7.5%). Conclusions: In contrast to normal thymus, TETs had significantly higher levels of CD47 expression. Tumor samples with high CD47 expression were mostly WHO types A and AB. This is the first study to explore CD47 expression in thymic cancers and lends support for ongoing investigation of anti-CD47 macrophage checkpoint inhibitor therapy in these tumors.

Safety, immunogenicity and efficacy of an mRNA-based COVID-19 vaccine, GLB-COV2-043, in preclinical animal models.

Several COVID-19 vaccines, some more efficacious than others, are now available and deployed, including multiple mRNA- and viral vector-based vaccines. With the focus on creating cost-effective solutions that can reach the low- and medium- income world, GreenLight Biosciences has developed an mRNA vaccine candidate, GLB-COV2-043, encoding for the full-length SARS-CoV-2 Wuhan wild-type spike protein. In pre-clinical studies in mice, GLB-COV2-043 induced robust antigen-specific binding and virus-neutralizing antibody responses targeting homologous and heterologous SARS-CoV-2 variants and a TH1-biased immune response. Boosting mice with monovalent or bivalent mRNA-LNPs provided rapid recall and long-lasting neutralizing antibody titers, an increase in antibody avidity and breadth that was held over time and generation of antigen-specific memory B- and T- cells. In hamsters, vaccination with GLB-COV2-043 led to lower viral loads, reduced incidence of SARS-CoV-2-related microscopic findings in lungs, and protection against weight loss after heterologous challenge with Omicron BA.1 live virus. Altogether, these data indicate that GLB-COV2-043 mRNA-LNP vaccine candidate elicits robust protective humoral and cellular immune responses and establishes our mRNA-LNP platform for subsequent clinical evaluations.

Tonsillectomy and Adenoidectomy - Pediatric Clinics of North America.

Tonsillectomy and adenoidectomy are among the most commonly performed major pediatric operations in the United States, with more than 500,000 procedures performed annually. This procedure can be performed with or without adenoidectomy. These procedures were traditionally performed for recurrent tonsillitis; however, the vast majority of tonsillectomies are currently performed for obstructive symptoms. When performed for appropriate indications, tonsillectomy and adenoidectomy can greatly improve a child's quality of life and general health. Given the prevalence of these conditions and subsequent surgical procedures, evidence-based recommendations are regularly evaluated and updated. As such, familiarity with these guidelines is necessary for pediatric practitioners. This review summarizes the indications, complications, and outcomes for tonsillectomy and adenoidectomy, as well as provides a brief overview of operative techniques.