Pregnancy and Childbirth After Spinal Fusion for Adolescent Idiopathic Scoliosis.

BACKGROUND: Little data exist on pregnancy and childbirth for adolescent idiopathic scoliosis (AIS) patients treated with a spinal fusion. The current literature relies on data from patients treated with spinal fusion techniques and instrumentation, such as Harrington rods, that are no longer in use. The objective of our study is to understand the effects of spinal fusion in adolescence on pregnancy and childbirth. METHODS: Prospectively collected data of AIS patients undergoing posterior spinal fusion that were enrolled in a multicenter study who have had a pregnancy and childbirth were reviewed. Results were summarized using descriptive statistics and compared with national averages using χ 2 test of independence. RESULTS: A total of 78 babies were born to 53 AIS patients. As part of their pre-natal care, 24% of patients surveyed reported meeting with an anesthesiologist before delivery. The most common types of delivery were spontaneous vaginal delivery (46%, n=36/78) and planned cesarean section (20%, n=16/78). Compared with the national average, study patients had a higher rate of cesarean delivery ( P =0.021). Of the women who had a spontaneous vaginal birth, 53% had no anesthesia (n=19/36), 19% received intravenous intermittent opioids (n=7/36), and 31% had regional spinal or epidural anesthesia (n=11/36). spontaneous vaginal delivery patients in our study cohort received epidural or spinal anesthesia less frequently than the national average ( P <0.001). Of those (n=26 pregnancies) who did not have regional anesthesia (patients who had no anesthesia or utilized IV intermittent opioids), 19% (n=5 pregnancies) were told by their perinatal providers that it was precluded by previous spine surgery. CONCLUSION: The majority of AIS patients reported not meeting with an anesthesiologist before giving birth and those who had a planned C-section did so under obstetrician recommendation. The presence of instrumentation after spinal fusion should be avoided with attempted access to the spinal canal but should not dictate a delivery plan. A multidisciplinary team consisting of obstetrician, anesthesiologist, and orthopaedic surgeon can provide the most comprehensive information to empower a patient to make her decisions regarding birth experience anesthesia based on maternal rather than provider preference. LEVEL OF EVIDENCE: IV.

The prognostic impact of t(11;14) in multiple myeloma: A real-world analysis from the Australian Lymphoma Leukaemia Group (ALLG) and the Australian Myeloma and Related Diseases Registry (MRDR).

The prognostic impact of t(11;14) in multiple myeloma (MM) needs to be better understood to inform future treatment decisions. The Australian Lymphoma Leukaemia Group embarked on a retrospective, observational cohort study using real-world data to interrogate treatment patterns and outcomes in 74 MM patients with t(11;14) [t(11;14)-MM] diagnosed over 10 years. This was compared to 159 and 111 MM patients with high-risk IgH translocations (IgH HR-MM) and hyperdiploidy (Hyperdiploid-MM), respectively, from the Australian Myeloma and Related Diseases Registry. No appreciable differences in age, gender, ISS, LDH levels, 1q21 or del(17p) status, or treatment patterns were observed between groups. Median PFS-1 was not different between groups but both t(11;14)-MM and IgH HR-MM had an inferior PFS-2 vs. Hyperdiploid-MM: median PFS-2 8.2 months, 10.0 months, and 19.8 months (p = 0.002), respectively. The 3-year OS were 69%, 71%, and 82% (p = 0.026), respectively. In the t(11;14)-MM group, gain or amplification of 1q21 at diagnosis predicted for poorer OS (HR 3.46, p = 0.002). Eleven patients had received venetoclax with 45% achieving better than a very good partial response. Results suggest that t(11;14) MM may confer an unfavorable risk profile and that the use of targeted therapies such as venetoclax earlier in the treatment algorithm should be explored.

Development of a Survey Tool: Understanding the Patient Experience With Personalized 3D Models in Surgical Patient Education.

BACKGROUND: Three-dimensional (3D) printing has been increasingly utilized in the healthcare sector for many applications including guiding surgical procedures, creating medical devices, and producing custom prosthetics. As personalized medicine becomes more accessible and desired, 3D printed models emerge as a potential tool in providing patient-specific education. These personalized 3D models are at the intersection of technological innovation and medical education. Our study group utilized a modified Delphi process to create a comprehensive survey tool assessing patient experience with personalized 3D models in preoperative education. METHODS: A rigorous literature review was conducted of prior patient education survey tools in surgical cases across specialties involving personalized 3D printed models. Through categorization and mapping, a core study team reviewed individual questions, removed duplicates, and edited them into generalizable form. A modified Delphi process was then used to solicit feedback on question clarity and relevance from both 3D printing healthcare experts and patients to create a final survey.  Results: 173 survey questions from the literature were evaluated by the core study team, yielding 31 unique questions for further review. After multiple rounds of feedback, a final survey containing 18 questions was developed.  Conclusion: 3D printed models have the potential to be helpful tools in surgical patient education, and there exists a need to standardize the assessment of patient experience with these models. This survey provides a standardized, generalizable way to investigate the patient experience with personalized 3D-printed models.

The use of individualized 3D-printed models on trainee and patient education, and surgical planning for robotic partial nephrectomies.

3D printing is a growing tool in surgical education to visualize and teach complex procedures. Previous studies demonstrating the usefulness of 3D models as teaching tools for partial nephrectomy used highly detailed models costing between $250 and 1000. We aimed to create thorough, inexpensive 3D models to accelerate learning for trainees and increase health literacy in patients. Patient-specific, cost-effective ($30-50) 3D models of the affected urologic structures were created using pre-operative imaging of 40 patients undergoing partial nephrectomy at Thomas Jefferson University Hospital (TJUH) between July 2020 and May 2021. Patients undergoing surgery filled out a survey before and after seeing the model to assess patient understanding of their kidney, pathophysiology, surgical procedure, and risks of surgery. Three urological residents, one fellow, and six attendings filled out separate surveys to assess their surgical plan and confidence before and after seeing the model. In a third survey, they ranked how much the model helped their comprehension and confidence during surgery. Patient understanding of all four subjects significantly improved after seeing the 3D model (P < 0.001). The urology residents (P < 0.001) and fellow (P < 0.001) reported significantly increased self-confidence after interacting with the model. Attending surgeon confidence increased significantly after seeing the 3D model (P < 0.01) as well. Cost-effective 3D models are effective learning tools and assist with the evaluation of patients presenting with renal masses, and increase patient, resident, and fellow understanding in partial nephrectomies. Further research should continue to explore the utility of inexpensive models in other urologic procedures.

Standardizing evaluation of patient-specific 3D printed models in surgical planning: development of a cross-disciplinary survey tool for physician and trainee feedback.

BACKGROUND: 3D printed models are becoming increasingly popular in healthcare as visual and tactile tools to enhance understanding of anatomy and pathology in medical trainee education, provide procedural simulation training, and guide surgical procedures. Patient-specific 3D models are currently being used preoperatively for trainee medical education in planning surgical approaches and intraoperatively to guide decision-making in several specialties. Our study group utilized a modified Delphi process to create a standardized assessment for trainees using patient-specific 3D models as a tool in medical education during pre-surgical planning. METHODS: A literature review was conducted to identify survey questions administered to clinicians in published surgical planning studies regarding the use of patient-specific 3D models. A core study team reviewed these questions, removed duplicates, categorized them, mapped them to overarching themes, and, where applicable, modified individual questions into a form generalizable across surgical specialties. The core study panel included a physician, physician-scientist, social scientist, engineer/medical student, and 3D printing lab manager. A modified Delphi process was then used to solicit feedback on the clarity and relevance of the individual questions from an expert panel consisting of 12 physicians from specialties including anesthesiology, emergency medicine, radiology, urology, otolaryngology, and obstetrics/gynecology. When the Radiological Society of North America (RSNA)/American College of Radiology (ACR) 3D Printing Registry Data Dictionary was released, additional survey questions were reviewed. A final cross-disciplinary survey of the utility of 3D printed models in surgical planning medical education was developed. RESULTS: The literature review identified 100 questions previously published in surveys assessing patient-specific 3D models for surgical planning. Following the review, generalization, and mapping of survey questions from these studies, a list of 24 questions was generated for review by the expert study team. Five additional questions were identified in the RSNA/ACR 3D Printing Registry Data Dictionary and included for review. A final questionnaire consisting of 20 questions was developed. CONCLUSIONS: As 3D printed models become more common in medical education, the need for standardized assessment is increasingly essential. The standardized questionnaire developed in this study reflects the interests of a variety of stakeholders in patient-specific 3D models across disciplines.

Genetic regulation of OAS1 nonsense-mediated decay underlies association with COVID-19 hospitalization in patients of European and African ancestries.

The chr12q24.13 locus encoding OAS1-OAS3 antiviral proteins has been associated with coronavirus disease 2019 (COVID-19) susceptibility. Here, we report genetic, functional and clinical insights into this locus in relation to COVID-19 severity. In our analysis of patients of European (n = 2,249) and African (n = 835) ancestries with hospitalized versus nonhospitalized COVID-19, the risk of hospitalized disease was associated with a common OAS1 haplotype, which was also associated with reduced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance in a clinical trial with pegIFN-λ1. Bioinformatic analyses and in vitro studies reveal the functional contribution of two associated OAS1 exonic variants comprising the risk haplotype. Derived human-specific alleles rs10774671-A and rs1131454 -A decrease OAS1 protein abundance through allele-specific regulation of splicing and nonsense-mediated decay (NMD). We conclude that decreased OAS1 expression due to a common haplotype contributes to COVID-19 severity. Our results provide insight into molecular mechanisms through which early treatment with interferons could accelerate SARS-CoV-2 clearance and mitigate against severe COVID-19.

From the ground up: understanding the developing infrastructure and resources of 3D printing facilities in hospital-based settings.

BACKGROUND: 3D printing is a popular technology in many industries secondary to its ability to rapidly produce inexpensive, high fidelity models/products, mainly through layer-by-layer fusion of various substrate materials. In healthcare, 3D printing has garnered interest for its applications in surgery, simulation, education, and medical device development, and 3D printing facilities are now being integrated into hospital-based settings. Yet, little is known regarding the leadership, resources, outputs, and role of these new onsite entities. METHODS: The purpose of this research was to survey features of North American hospital-based 3D printing facilities to understand their design and utility in anticipation of future expansion. Hospital-based 3D printing labs were recruited through online special interest groups to participate via survey response. Anonymous, voluntary data were collected from 21 facilities over 9 weeks and reported/analyzed in aggregate. RESULTS: Of the respondents, > 50% were founded in the past 5 years and 80% in the past decade, indicating recent and rapid growth of such facilities. Labs were most commonly found within large, university-affiliated hospitals/health systems with administration frequently, but not exclusively, through radiology departments, which was shown to enhance collaboration. All groups reported collaborating with other medical specialties/departments and image segmentation as part of the workflow, showing widespread interest in high fidelity, personalized medicine applications. Lab leadership was most often multidisciplinary, with physicians present on nearly all leadership teams. Budgets, personnel, and outputs varied among groups, however, all groups reported engagement in multiple 3D printing applications. CONCLUSION: This preliminary study provides a foundation for understanding the unique nature of hospital-based 3D printing labs. While there is much to learn about such in-house facilities, the data obtained reveal important baseline characteristics. Further research is indicated to validate these early findings and create a detailed picture of the developing infrastructure of 3D printing in healthcare settings.

Development and evaluation of a community of practice to improve stem cell donor recruitment in Canada.

Background and Objectives Communities of practice (CoPs) represent effective models to achieve quality outcomes in health care. We report the development and evaluation of a CoP to improve stem cell donor recruitment in Canada. Materials and Methods In September 2017, we invited national stakeholders in stem cell donor recruitment to participate in a Facebook group and regular e-meetings. E-meetings involved speakers and roundtable discussion on topics related to donor recruitment. The Facebook group facilitated sharing of resources. We evaluated stakeholder perspective of the CoP and the impact on recruitment outcomes. Results As of December 2020, the CoP included 382 members who published 243 posts to the Facebook group about patient/donor stories (40%), resources (27%), updates/questions (21%) and recruitment outcomes (12%). In January 2020, we surveyed 44 CoP participants; the majority felt that the Facebook group (86%) and e-meetings (59%) supported the community, and that the CoP fostered collaboration (82%), improved their donor recruitment knowledge (75%) and practice (77%) and improved their ability to recruit needed donors (64%). The launch of the CoP correlated with improved donor recruitment outcomes. In 2016-2017, CoP participants recruited 2918 registrants (46% male; 55.9% non-Caucasian) compared to 4531 registrants in 2018-2019 (52.9% male; 62.7% non-Caucasian). Members of the CoP developed innovative resources to support recruitment efforts and led national campaigns securing coverage in major media outlets. Conclusion We describe the first CoP in stem cell donor recruitment to be formally evaluated. The CoP model may be adopted by donor recruitment organisations, registries and blood banks worldwide to improve recruitment outcomes. HIGHLIGHTS: • A community of practice (CoP) in stem cell donor recruitment was valued by participants and supported efforts to improve recruitment outcomes. • The CoP model may be adopted by donor recruitment organizations, donor registries, and blood banks worldwide to improve recruitment outcomes.

Techniques for Developing and Assessing Immune Responses Induced by Synthetic DNA Vaccines for Emerging Infectious Diseases.

Vaccines are one of mankind's greatest medical advances, and their use has drastically reduced and in some cases eliminated (e.g., smallpox) disease and death caused by infectious agents. Traditional vaccine modalities including live-attenuated pathogen vaccines, wholly inactivated pathogen vaccines, and protein-based pathogen subunit vaccines have successfully been used to create efficacious vaccines against measles, mumps, rubella, polio, and yellow fever. These traditional vaccine modalities, however, take many months to years to develop and have thus proven less effective for use in creating vaccines to emerging or reemerging infectious diseases (EIDs) including influenza, Human immunodeficiency virus (HIV), dengue virus (DENV), chikungunya virus (CHIKV), West Nile virus (WNV), Middle East respiratory syndrome (MERS), and the severe acute respiratory syndrome coronaviruses 1 and 2 (SARS-CoV and SARS-CoV-2). As factors such as climate change and increased globalization continue to increase the pace of EID development, newer vaccine modalities are required to develop vaccines that can prevent or attenuate EID outbreaks throughout the world. One such modality, DNA vaccines, has been studied for over 30 years and has numerous qualities that make them ideal for meeting the challenge of EIDs including; (1) DNA vaccine candidates can be designed within hours of publishing of a pathogens genetic sequence; (2) they can be manufactured cheaply and rapidly in large quantities; (3) they are thermostable and have reduced requirement for a cold-chain during distribution, and (4) they have a remarkable safety record in the clinic. Optimizations made in plasmid design as well as in DNA vaccine delivery have greatly improved the immunogenicity of these vaccines. Here we describe the process of making a DNA vaccine to an EID pathogen and describe methods used for assessing the immunogenicity and protective efficacy of DNA vaccines in small animal models.

Development of Siglec-9 Blocking Antibody to Enhance Anti-Tumor Immunity.

Sialic acid-binding Immunoglobulin-like lectin-9 (Siglec-9) is a glyco-immune negative checkpoint expressed on several immune cells. Siglec-9 exerts its inhibitory effects by binding to sialoglycan ligands expressed on cancer cells, enabling them to evade immunosurveillance. We developed a panel of human anti-Siglec-9 hybridoma clones by immunizing mice with Siglec-9-encoding DNA and Siglec-9 protein. The lead antibodies, with high specificity and functionality against Siglec-9, were identified through screening of clones. The in vitro cytotoxicity assays showed that our lead antibody enhances anti-tumor immune activity. Further, in vivo testing utilizing ovarian cancer humanized mouse model showed a drastic reduction in tumor volume. Together, we developed novel antibodies that augment anti-tumor immunity through interference with Siglec-9-mediated immunosuppression.

Siglec-9 defines and restrains a natural killer subpopulation highly cytotoxic to HIV-infected cells.

Siglec-9 is an MHC-independent inhibitory receptor expressed on a subset of natural killer (NK) cells. Siglec-9 restrains NK cytotoxicity by binding to sialoglycans (sialic acid-containing glycans) on target cells. Despite the importance of Siglec-9 interactions in tumor immune evasion, their role as an immune evasion mechanism during HIV infection has not been investigated. Using in vivo phenotypic analyses, we found that Siglec-9+ CD56dim NK cells, during HIV infection, exhibit an activated phenotype with higher expression of activating receptors and markers (NKp30, CD38, CD16, DNAM-1, perforin) and lower expression of the inhibitory receptor NKG2A, compared to Siglec-9- CD56dim NK cells. We also found that levels of Siglec-9+ CD56dim NK cells inversely correlate with viral load during viremic infection and CD4+ T cell-associated HIV DNA during suppressed infection. Using in vitro cytotoxicity assays, we confirmed that Siglec-9+ NK cells exhibit higher cytotoxicity towards HIV-infected cells compared to Siglec-9- NK cells. These data are consistent with the notion that Siglec-9+ NK cells are highly cytotoxic against HIV-infected cells. However, blocking Siglec-9 enhanced NK cells' ability to lyse HIV-infected cells, consistent with the known inhibitory function of the Siglec-9 molecule. Together, these data support a model in which the Siglec-9+ CD56dim NK subpopulation is highly cytotoxic against HIV-infected cells even whilst being restrained by the inhibitory effects of Siglec-9. To harness the cytotoxic capacity of the Siglec-9+ NK subpopulation, which is dampened by Siglec-9, we developed a proof-of-concept approach to selectively disrupt Siglec/sialoglycan interactions between NK and HIV-infected cells. We achieved this goal by conjugating Sialidase to several HIV broadly neutralizing antibodies. These conjugates selectively desialylated HIV-infected cells and enhanced NK cells' capacity to kill them. In summary, we identified a novel, glycan-based interaction that may contribute to HIV-infected cells' ability to evade NK immunosurveillance and developed an approach to break this interaction.

N-terminal serine/threonine motif has diverse and important effects on behavior of multiple AAV serotypes.

Adeno-associated virus (AAV) is a promising gene therapy vector, but questions remain regarding mechanisms of basic viral functions. We previously showed that a serine/threonine (S/T) triplet motif and its flanking residues, located in the overlapping N-terminus of VP1/VP2 and highly conserved across most AAV serotypes, are critical for viral transcript production in vitro. Here we generate a panel of S/T triplet mutants in AAV serotypes 2, 4, and 9 and characterize their behaviors in vitro and in vivo using next generation sequencing. We show that S/T triplet mutations can significantly hinder some stages of transduction in a serotype-dependent manner in vitro. Interestingly, these defects are largely overcome in C57BL/6 mice, with only one mutant displaying altered behavior in vivo. Taken together, our results identify a short N-terminal capsid motif with diverse roles across several AAV serotypes which better informs engineering efforts to improve AAV as a vector for gene therapy.

Family Members' Perceptions of Their Psychological Responses One Year Following Pediatric Intensive Care Unit (PICU) Hospitalization: Qualitative Findings From the Caring Intensively Study.

Introduction: PICU hospitalization can have a profound impact on child survivors and their families. There is limited research on children's long-term recovery within the context of the family following critical illness. This study aimed to explore children's and parents' perceptions of long-term psychological and behavioral responses within the context of the family one year following PICU hospitalization. Materials and Methods: Caring Intensively is a mixed methods multi-site prospective cohort study that aims to examine children's psychological and behavioral responses over a 3-year period following PICU hospitalization. In this study, part of the qualitative arm of Caring Intensively, an interpretive descriptive design was used to explore children's recovery one year post-discharge. Purposive sampling was used to select 17 families, including 16 mothers, 6 fathers, and 9 children. Semi-structured, audio-recorded interviews were conducted. Data were analyzed iteratively using the constant comparison method. Results: Families described efforts to readapt to routine life and find a new normal following PICU hospitalization. Finding a New Normal consisted of four major themes: (1) Processing PICU Reminders and Memories, (2) Changing Perceptions of Health and Illness, (3) We Are Not the Same, and (4) Altered Relationships. Participants described significant emotional and behavioral changes during the year following discharge. The psychological impact of individual family members' experiences led to changes in their sense of self, which affected family dynamics. PICU memories and reminders impacted participants' perceptions of childhood health and illness and resulted in increased vigilance. Parents and siblings demonstrated increased concern for the child survivor's health, and the experience of long absences and new or altered caregiving roles resulted in changes in relationships and family dynamics. Conclusion: PICU hospitalization impacted the psychological well-being of all family members as they sought to re-establish a sense of normalcy one year following discharge. Parent and child experiences and responses were closely interconnected. Findings highlight the importance of increased follow-up care aimed at supporting the family's psychological recovery.

Identification of Novel Neutralizing Monoclonal Antibodies against SARS-CoV-2 Spike Glycoprotein.

Coronavirus disease 2019 (COVID-19) is caused by the newly emerged human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to the highly contagious nature of SARS-CoV-2, it has infected more than 137 million individuals and caused more than 2.9 million deaths globally as of April 13, 2021. There is an urgent need to develop effective novel therapeutic strategies to treat or prevent this infection. Toward this goal, we focused on the development of monoclonal antibodies (mAbs) directed against the SARS-CoV-2 spike glycoprotein (SARS-CoV-2 Spike) present on the surface of virus particles as well as virus-infected cells. We isolated anti-SARS-CoV-2 Spike mAbs from animals immunized with a DNA vaccine. We then selected a highly potent set of mAbs against SARS-CoV-2 Spike protein and evaluated each candidate for their expression, target binding affinity, and neutralization potential using complementary ACE2-blocking and pseudovirus neutralization assays. We identified a total of 10 antibodies, which specifically and strongly bound to SARS-CoV-2 Spike, blocked the receptor binding domain (RBD) and angiotensin-converting enzyme 2 (ACE2) interaction, and neutralized SARS-CoV-2. Furthermore, the glycomic profile of the antibodies suggested that they have high Fc-mediated effector functions. These antibodies should be further investigated for elucidating the neutralizing epitopes on Spike for the design of next-generation vaccines and for their potential in diagnostic as well as therapeutic utilities against SARS-CoV-2.

Genetic regulation of OAS1 nonsense-mediated decay underlies association with risk of severe COVID-19.

Genomic regions have been associated with COVID-19 susceptibility and outcomes, including the chr12q24.13 locus encoding antiviral proteins OAS1-3. Here, we report genetic, functional, and clinical insights into genetic associations within this locus. In Europeans, the risk of hospitalized vs. non-hospitalized COVID-19 was associated with a single 19Kb-haplotype comprised of 76 OAS1 variants included in a 95% credible set within a large genomic fragment introgressed from Neandertals. The risk haplotype was also associated with impaired spontaneous but not treatment-induced SARS-CoV-2 clearance in a clinical trial with pegIFN-λ1. We demonstrate that two exonic variants, rs10774671 and rs1131454, affect splicing and nonsense-mediated decay of OAS1 . We suggest that genetically-regulated loss of OAS1 expression contributes to impaired spontaneous clearance of SARS-CoV-2 and elevated risk of hospitalization for COVID-19. Our results provide the rationale for further clinical studies using interferons to compensate for impaired spontaneous SARS-CoV-2 clearance, particularly in carriers of the OAS1 risk haplotypes.

Permeabilizing Cell Membranes with Electric Fields.

The biological impact of exogenous, alternating electric fields (AEFs) and direct-current electric fields has a long history of study, ranging from effects on embryonic development to influences on wound healing. In this article, we focus on the application of electric fields for the treatment of cancers. In particular, we outline the clinical impact of tumor treating fields (TTFields), a form of AEFs, on the treatment of cancers such as glioblastoma and mesothelioma. We provide an overview of the standard mechanism of action of TTFields, namely, the capability for AEFs (e.g., TTFields) to disrupt the formation and segregation of the mitotic spindle in actively dividing cells. Though this standard mechanism explains a large part of TTFields' action, it is by no means complete. The standard theory does not account for exogenously applied AEFs' influence directly upon DNA nor upon their capacity to alter the functionality and permeability of cancer cell membranes. This review summarizes the current literature to provide a more comprehensive understanding of AEFs' actions on cell membranes. It gives an overview of three mechanistic models that may explain the more recent observations into AEFs' effects: the voltage-gated ion channel, bioelectrorheological, and electroporation models. Inconsistencies were noted in both effective frequency range and field strength between TTFields versus all three proposed models. We addressed these discrepancies through theoretical investigations into the inhomogeneities of electric fields on cellular membranes as a function of disease state, external microenvironment, and tissue or cellular organization. Lastly, future experimental strategies to validate these findings are outlined. Clinical benefits are inevitably forthcoming.

Surgical and Radiological Management of Complicated Uterine Leiomyoma Aided by 3D Models in a Patient with Fibrodysplasia Ossificans Progressiva.

BACKGROUND Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder of the connective tissue. Over time, patients with FOP experience decreased range of motion in the joints and the formation of a second skeleton, limiting mobility. Patients with FOP are advised to avoid any unwarranted surgery owing to the risk of a heterotopic ossification flare-up. For patients who do require a surgical procedure, a multidisciplinary team is recommended for comprehensive management of the patient's needs. CASE REPORT A 27-year-old woman with FOP underwent a hysterectomy for removal of a suspected necrotic uterine fibroid. To aid in presurgical planning and management, patient-specific 3-dimensional (3D) models of the patient's tracheobronchial tree, thorax, and lumbosacral spine were printed from the patient's preoperative computed tomography (CT) imaging. The patient required awake nasal fiberoptic intubation for general anesthesia and transversus abdominus plane block for regional anesthesia. Other anesthesia modalities, including spinal epidural, were ruled out after visualizing the patient's anatomy using the 3D model. Postoperatively, the patient was started on a multi-modal analgesic regimen and a course of steroids, and early ambulation was encouraged. CONCLUSIONS Patients with FOP are high-risk surgical patients requiring the care of multiple specialties. Advanced visualization methods, including 3D printing, can be used to better understand their anatomy and locations of heterotopic bone ossification that can affect patient positioning. Our patient successfully underwent supracervical hysterectomy and bilateral salpingectomy with no signs of fever or sepsis at follow-up.

Landscape of humoral immune responses against SARS-CoV-2 in patients with COVID-19 disease and the value of antibody testing.

A new pandemic is ongoing in several parts of the world. The agent responsible is the newly emerged severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The symptoms associated with this virus are known as the coronavirus disease-2019 (COVID-19). In this review, we summarize the published data on virus specific antibodies in hospitalized patients with COVID-19 disease, patients recovered from the disease and the individuals who are asymptomatic with SARS-CoV-2 infections. The review highlights the following: i) an adjunct role of antibody tests in the diagnosis of COVID-19 in combination with RT-PCR; ii) status of antibodies from COVID-19 convalescent patients to select donors for plasma therapy; iii) the potential confounding effects of other coronaviruses, measles, mumps and rubella in antibody testing due to homology of certain viral genes; and iv) the role of antibody testing for conducting surveillance in populations, incidence estimation, contact tracing and epidemiologic studies.

Immunotherapy of prostate cancer using novel synthetic DNA vaccines targeting multiple tumor antigens.

Prostate cancer is a prevalent cancer in men and consists of both indolent and aggressive phenotypes. While active surveillance is recommended for the former, current treatments for the latter include surgery, radiation, chemo and hormonal therapy. It has been observed that the recurrence in the treated patients is high and results in castration resistant prostate cancer for which treatment options are limited. This scenario has prompted us to consider immunotherapy with synthetic DNA vaccines, as this approach can generate antigen-specific tumor-killing immune cells. Given the multifocal and heterogeneous nature of prostate cancer, we hypothesized that synthetic DNA vaccines targeting different prostate specific antigens are likely to induce broader and improved immunity who are at high risk as well as advanced clinical stage of prostate cancer, compared to a single antigen approach. Utilizing a bioinformatics approach, synthetic enhanced DNA vaccine (SEV) constructs were generated against STEAP1, PAP, PARM1, PSCA, PCTA and PSP94. Synthetic enhanced vaccines for prostate cancer antigens were shown to elicit antigen-specific immune responses in mice and the anti-tumor activity was evident in a prostate tumor challenge mouse model. These studies support further evaluation of the DNA tools for immunotherapy of prostate cancer and perhaps other cancers.

F5-Atlanta: A novel mutation in F5 associated with enhanced East Texas splicing and FV-short production.

BACKGROUND: Elucidating the molecular pathogenesis underlying East Texas bleeding disorder (ET) led to the discovery of alternatively spliced F5 transcripts harboring large deletions within exon 13. These alternatively spliced transcripts produce a shortened form of coagulation factor V (FV) in which a large portion of its B-domain is deleted. These FV isoforms bind tissue factor pathway inhibitor alpha (TFPIα) with high affinity, prolonging its circulatory half-life and enhancing its anticoagulant effects. While two missense pathogenic variants highlighted this alternative splicing event, similar internally deleted FV proteins are found in healthy controls. OBJECTIVE: We identified a novel heterozygous 832 base pair deletion within F5 exon 13, termed F5-Atlanta (F5-ATL), in a patient with severe bleeding. Our objective is to investigate the effect of this deletion on F5 and FV expression. METHODS & RESULTS: Assessment of patient plasma revealed markedly elevated levels of total and free TFPI and a FV isoform similar in size to the FV-short described in ET. Sequencing analyses of cDNA revealed the presence of a transcript alternatively spliced using the ET splice sites, thereby removing the F5-ATL deletion. This alternative splicing pattern was recapitulated by heterologous expression in mammalian cells. CONCLUSIONS: These findings support a mechanistic model consisting of cis-acting regulatory sequences encoded within F5 exon 13 that control alternative splicing at the ET splice sites and thereby regulate circulating FV-short and TFPIα levels.