ß3-adrenergic agonist counters oxidative stress and Na+-K+ pump inhibitory S-glutathionylation of placental cells: Implications for preeclampsia.

Oxidative stress from placental ischemia/reperfusion and hypoxia/reoxygenation (H/R) in preeclampsia is accompanied by Na+-K+ pump inhibition and S-glutathionylation of its ß1 subunit (GSS-ß1), a modification that inhibits the pump. ß3-adrenergic receptor (ß3-AR) agonists can reverse GSS-ß1. We examined effects of the agonist CL316,243 on GSS-ß1 and sources of H/R-induced oxidative stress in immortalized first trimester human trophoblast (HTR-8/SVneo) and freshly isolated placental explants from normal term pregnancies. H/R increased GSS-ß1 and, reflecting compromised α1/ß1 subunit interaction, it reduced α1/ß1 pump subunit co-immunoprecipitation. H/R increased p47phox/p22phox NADPH oxidase subunit co-immunoprecipitation reflecting membrane translocation of cytosolic p47phox that is needed to activate NADPH oxidase. Fluorescence of O2•--sensitive dihydroethidium increased in parallel. H/R increased S-glutathionylation of endothelial nitric oxide synthase (GSS-eNOS) that uncouples NO synthesis towards synthesis of O2•- and reduced trophoblast migration. Oxidative stress induced by tumor necrosis factor α (TNF-α) increased soluble fms-like tyrosine kinase receptor 1 (sFlt-1) trophoblast release, a marker of preeclampsia, and reduced trophoblast integration into endothelial cellular networks. CL316,243 eliminated H/R-induced GSS-ß1 and decreases of α1/ß1 subunit coimmunoprecipitation, eliminated NADPH oxidase activation and increases in GSS-eNOS, restored trophoblast migration, eliminated increased sFlt-1 release and restored trophoblast integration in endothelial cell networks. H/R induced GSS-ß1, α1/ß1 subunit co-immunoprecipitation and NADPH oxidase activation of placental explants reflected effects of H/R for trophoblasts and CL316,243 eliminated these changes. We conclude a ß3-AR agonist counters key pathophysiological features of preeclampsia in vitro. ß3 agonists already in human use for another purpose are potential candidates for re-purposing to treat preeclampsia.

MR Lymphangiography in Lymphatic Disorders: Clinical Applications, Institutional Experience, and Practice Development.

Lymphatic flow and anatomy can be challenging to study, owing to variable lymphatic anatomy in patients with diverse primary or secondary lymphatic pathologic conditions and the fact that lymphatic imaging is rarely performed in healthy individuals. The primary components of the lymphatic system outside the head and neck are the peripheral, retroperitoneal, mesenteric, hepatic, and pulmonary lymphatic systems and the thoracic duct. Multiple techniques have been developed for imaging components of the lymphatic system over the past century, with trade-offs in spatial, temporal, and contrast resolution; invasiveness; exposure to ionizing radiation; and the ability to obtain information on dynamic lymphatic flow. More recently, dynamic contrast-enhanced (DCE) MR lymphangiography (MRL) has emerged as a valuable tool for imaging both lymphatic flow and anatomy in a variety of congenital and acquired primary or secondary lymphatic disorders. The authors provide a brief overview of lymphatic physiology, anatomy, and imaging techniques. Next, an overview of DCE MRL and the development of an MRL practice and workflow in a hybrid interventional MRI suite incorporating cart-based in-room US is provided, with an emphasis on multidisciplinary collaboration. The spectrum of congenital and acquired lymphatic disorders encountered early in an MRL practice is provided, with emphasis on the diversity of imaging findings and how DCE MRL can aid in diagnosis and treatment of these patients. Methods such as DCE MRL for assessing the hepatic and mesenteric lymphatic systems and emerging technologies that may further expand DCE MRL use such as three-dimensional printing are introduced. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Safety and histopathologic yield of percutaneous CT-guided biopsies of the skull base, orbit, and calvarium.

PURPOSE: Although CT-guided biopsies of the calvarium, skull base, and orbit are commonly performed, the best approaches, efficacy, and safety of such procedures remain scantly described in the literature. This retrospective review of percutaneous biopsies illustrates several approaches to challenging biopsy targets and provides a review of procedural planning considerations and histopathologic yield. METHODS: A retrospective review of CT-guided biopsies of the skull base, calvarium, and orbit between 1/1/2010 and 10/30/2020 was conducted. Patient demographics and procedural factors were recorded, including lesion size and location, biopsy approach, and needle gauge. Outcomes were also noted, including CT dose length product, complications, and histopathologic yield. RESULTS: Sixty-one CT-guided biopsies were included in the final analysis: 34 skull base, 23 calvarial, and 4 orbital lesions. The initial diagnostic yield was 32/34 (94%) for skull base lesions, with one false-negative and one non-diagnostic sample. Twenty-one of twenty-three (91%) biopsies in the calvarium were initially diagnostic, with one false-negative and one non-diagnostic sample. In the orbit, 4/4 biopsies were diagnostic. The total complication rate for the cohort was 4/61 (6.6%). Three complications were reported in skull base procedures (2 immediate and 1 delayed). A single complication was reported in a calvarial biopsy, and no complications were reported in orbital biopsies. CONCLUSION: Percutaneous CT-guided core needle biopsies can be performed safely and with a high diagnostic yield for lesions in the skull base, calvarium, and orbit.

Patient-specific Implants Improve Volumetric Surgical Accuracy Compared to Stock Reconstruction Plates in Modern Paradigm Virtual Surgical Planning of Fibular Free Flaps for Head and Neck Reconstruction.

BACKGROUND: Virtual surgical planning (VSP) for composite microvascular free flaps has become standard of care for oncologic head and neck reconstruction. Controversy remains as to the use of three-dimensional (3D)-printed patient-specific titanium implants (PSIs) versus hand-bent stock reconstruction plates. Proponents of PSIs cite improved surgical accuracy, reduced operative times, and improved clinical outcomes. Detractors purport increased cost associated with PSIs and presumed equivalent accuracy with less expensive stock plates. PURPOSE: The study purpose was to measure and compare the 3D-volumetric accuracy of PSI versus stock reconstruction plates among subjects undergoing VSP-guided mandibular fibular free flap reconstruction. STUDY DESIGN, SETTING, SAMPLE: A retrospective cohort study of subjects undergoing VSP-guided fibular free flap reconstructions at Mayo Clinic between 2016 and 2023 was performed. Subjects were excluded for non-VSP guidance, midfacial reconstruction, nonfibular free flaps, and lack of requisite study variables. PREDICTOR VARIABLE: The primary predictor was the type of reconstruction plate utilized (PSI vs stock plate). MAIN OUTCOME VARIABLE: The main outcome was volumetric surgical accuracy of the final reconstruction compared to the preoperative surgical plan by root mean square error (RMSE) calculation. Lower RMSE values indicated a higher surgical accuracy. COVARIATES: Covariates included age, sex, race, smoking status, American Society of Anesthesiologists (ASA) Physical Status Classification System, Charlson Comorbidity Index, preoperative diagnosis, and number of fibular segments. ANALYSES: Differences in surgical accuracy were assessed between preoperative and postoperative segmented scans using volumetric overlays from which RMSE values were calculated. Univariate and multivariate modeling of plate type to RMSE calculation was performed. Statistical significance set to P < .05. RESULTS: Total of 130 subjects were identified, 105 PSI and 25 stock plates. Calculated mean RMSE in millimeters (mm) for stock plates was 1.46 (standard deviation: 0.33) and 1.15 (standard deviation: 0.36) for PSIs. Univariate modeling demonstrated a statistically significant difference in RMSE of 0.31 (95% confidence interval: 0.16-0.47) (P < .001) equating to a 21.2% (P < .001) improved volumetric surgical accuracy for PSIs. The association of improved volumetric accuracy with PSIs has been maintained in all multivariate models controlling for confounding. CONCLUSION AND RELEVANCE: In modern era VSP-guided head and neck fibular free flap reconstruction, patient-specific 3D-printed titanium implants confer a statistically significant improvement in volumetric surgical accuracy over stock reconstruction plates.

Intrapartum fetal heart rate monitoring: Rationalise, refine or replace?

Monitoring the fetal heartbeat underpins assessment of fetal wellbeing in labour. Although commonly employed in clinical practice, shortcomings remain. A recent review of clinical practice guidelines highlights the variation in definitions of the fetal heart rate that will lead to differences in interpretation. Will intrapartum care be improved by greater consensus around clinical practice guidelines through rationalisation or refinement of guidelines, or will the future see this technique replaced by more accurate forms of fetal monitoring?

Creation and Validation of a Novel 3-Dimensional Pediatric Hip Ultrasound Model.

OBJECTIVES: The aim of this study was to create and validate a 3-dimensional (3D) ultrasound model with normal and abnormal pediatric hip joint anatomy that is comparable to a pediatric hip joint in appearance and anatomy and replicates sonographic characteristics of a pediatric hip joint. METHODS: A 3D rendering of the bone and soft tissue was created from a computed tomography pelvic scan of a pediatric patient. This rendering was modified to include a unilateral joint effusion. The bone was 3D printed with a photopolymer plastic, whereas the soft tissue was cast with a silicone mixture in a 3D-printed mold. The effusion was simulated by injecting saline into the soft tissue cavity surrounding the bone. The ultrasound model was validated by pediatric point-of-care ultrasonographers at an international pediatric ultrasound conference. RESULTS: A pediatric hip ultrasound model was developed that simulates both normal and abnormal pediatric hip joint anatomy, each with an appropriately sized, measurable joint effusion. Validation by pediatric point-of-care ultrasonographers showed that the key aspects of a normal pediatric hip joint (femoral physis, sloped femoral neck, and adequate soft tissue) with an identifiable and measurable effusion were included in the ultrasound model. CONCLUSIONS: In this study, we successfully created a cost-effective, reusable, and reproducible 3D pediatric hip ultrasound model. The majority of pediatric point-of-care ultrasonographers who evaluated the model agreed that this model is comparable to a pediatric patient for the purpose of teaching ultrasound skills and joint space measurement.

Mandibular Gender Dimorphism: The Utility of Artificial Intelligence and Statistical Shape Modeling in Skeletal Facial Analysis.

BACKGROUND: In gender-affirming surgery, facial skeletal dimorphism is an important topic for every craniofacial surgeon. Few cephalometric studies have assessed this topic; however, they fall short to provide skeletal contour insights that direct surgical planning. Herein, we propose statistical shape modeling (SSM) as a novel tool for investigating mandibular dimorphism for young white individuals. METHODS: A single-center, retrospective study was performed using computed tomography (CT) scans of white individuals, aged 20 to 39 years old. AI-assisted, three-dimensional (3D) mandibles were reconstructed in Materialise Mimics v25.0. We used SSM to generate average 3D models for both genders. Relevant manual anthropometric measurements were taken for the SSMs and individual mandibles. Contour disparities were then represented using 3D overlays and heatmaps. Statistical analyses were performed using unpaired student t testing or Wilcoxon signed rank testing with 95% confidence interval as deemed appropriate by population-level normality assessment. RESULTS: Ninety-eight patients (53 females, 45 males) were included. Male mandibles showed greater bigonial width, intercondylar width, ramus height, and body length [p<0.005]. There was no statistically significant difference in the gonial angle measurements [p=0.62]. All relevant manual individual measurements demonstrated excellent concordance to their SSM counterparts. The 3D overlays of SSMs revealed squarer male chins with more lateral but less anterior projection than their female counterparts. Also, the female mandibles showed smoother transition at the gonial angle. CONCLUSIONS: SSM provides a novel tool to objectively evaluate volumetric and contour dimorphisms between genders. Moreover, this method can be automated, allowing for expedited comparisons between populations of interest compared to manual assessment. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266 . Bullet points about the importance of this work: Advancing Anthropometric Assessment: Statistical shape modeling (SSM) offers a cutting-edge approach to visualizing gender-specific skeletal anatomic differences for aesthetic and gender-affirming facial surgery. Expediting Comparative Analysis: The workflow established in this paper streamlines the evaluative process, enabling rapid morphologic comparisons between populations. Patient-Centered Care: This study establishes a foundation for the development of SSMs in individualized operative planning.

The Posterior Triangle and Posterior Muscles of the Neck in 3-Dimensions: Creating a Digital Anatomic Model Using Peer-Reviewed Literature, Radiographic Imaging, and an Experienced Medical Illustrator.

INTRODUCTION: The posterior cervical triangle houses an important nodal basin in the spread of several cancers in the head and neck, particularly cutaneous malignancies of the scalp. A safe and effective Level V neck dissection necessitates thorough understanding of the neurovascular structures housed within the region. Conventional 2D anatomical representations offer insights into the named structures, but fall short in illustrating the spatial relationships crucial in surgery. Here, we aim to develop an anatomically-precise 3D virtual model of the posterior cervical triangle and its constituent structures. METHODS: Musculature and neurovasculature were segmented from the computerized tomography (CT) angiogram of a healthy 29-year-old female. Literature review of cadaveric studies was performed to identify the most common variants, relevant surgical relationships, and usual dimensions of structures contained in the model. Structures unable to be visualized on imaging were created de novo using data obtained in the literature review. A medical illustrator then used this data to develop a 3D anatomical model using ZBrush. RESULTS: The musculature (sternocleidomastoid, trapezius, omohyoid, scalenes, erector spinae, and transversospinalis muscles) and neurovasculature (spinal accessory nerve, phrenic nerve, vertebral artery, subclavian artery, and brachial plexus) were characterized through literature review. Musculature and vasculature were segmented from CT angiography while neural structures were created de novo. Both radiographic and anatomic data were used to inform the creation of a 3D model, which will be uploaded to an online database for open access viewing. CONCLUSIONS: A dynamic understanding of the spatial relationships existing among structures housed within the posterior triangle of the neck is imperative when operating in the region. The development of an accurate 3D anatomical model of such structures based upon predominant variants found in the literature will supplement the education of practicing and aspiring head and neck surgeons.

Development and validation of a recursive partitioning analysis-based pretreatment decision-making tool identifying ideal candidates for spine stereotactic body radiation therapy.

BACKGROUND: This study was aimed at developing and validating a decision-making tool predictive of overall survival (OS) for patients receiving stereotactic body radiation therapy (SBRT) for spinal metastases. METHODS: Three hundred sixty-one patients at one institution were used for the training set, and 182 at a second institution were used for external validation. Treatments most commonly involved one or three fractions of spine SBRT. Exclusion criteria included proton therapy and benign histologies. RESULTS: The final model consisted of the following variables and scores: Spinal Instability Neoplastic Score (SINS) ≥ 6 (1), time from primary diagnosis < 21 months (1), Eastern Cooperative Oncology Group (ECOG) performance status = 1 (1) or ECOG performance status > 1 (2), and >1 organ system involved (1). Each variable was an independent predictor of OS (p < .001), and each 1-point increase in the score was associated with a hazard ratio of 2.01 (95% confidence interval [CI], 1.79-2.25; p < .0001). The concordance value was 0.75 (95% CI, 0.71-0.78). The scores were discretized into three groups-favorable (score = 0-1), intermediate (score = 2), and poor survival (score = 3-5)-with 2-year OS rates of 84% (95% CI, 79%-90%), 46% (95% CI, 36%-59%), and 21% (95% CI, 14%-32%), respectively (p < .0001 for each). In the external validation set (182 patients), the score was also predictive of OS (p < .0001). Increasing SINS was predictive of decreased OS as a continuous variable (p < .0001). CONCLUSIONS: This novel score is proposed as a decision-making tool to help to optimize patient selection for spine SBRT. SINS may be an independent predictor of OS.

Targeting alternative splicing as a new cancer immunotherapy-phosphorylation of serine arginine-rich splicing factor (SRSF1) by SR protein kinase 1 (SRPK1) regulates alternative splicing of PD1 to generate a soluble antagonistic isoform that prevents T cell exhaustion.

BACKGROUND: Regulation of alternative splicing is a new therapeutic approach in cancer. The programmed cell death receptor 1 (PD-1) is an immunoinhibitory receptor expressed on immune cells that binds to its ligands, PD-L1 and PD-L2 expressed by cancer cells forming a dominant immune checkpoint pathway in the tumour microenvironment. Targeting this pathway using blocking antibodies (nivolumab and pembrolizumab) is the mainstay of anti-cancer immunotherapies, restoring the function of exhausted T cells. PD-1 is alternatively spliced to form isoforms that are either transmembrane signalling receptors (flPD1) that mediate T cell death by binding to the ligand, PD-L1 or an alternatively spliced, soluble, variant that lacks the transmembrane domain. METHODS: We used PCR and western blotting on primary peripheral blood mononuclear cells (PBMCs) and Jurkat T cells, IL-2 ELISA, flow cytometry, co-culture of melanoma and cholangiocarcinoma cells, and bioinformatics analysis and molecular cloning to examine the mechanism of splicing of PD1 and its consequence. RESULTS: The soluble form of PD-1, generated by skipping exon 3 (∆Ex3PD1), was endogenously expressed in PBMCs and T cells and prevents cancer cell-mediated T cell repression. Multiple binding sites of SRSF1 are adjacent to PD-1 exon 3 splicing sites. Overexpression of phosphomimic SRSF1 resulted in preferential expression of flPD1. Inhibition of SRSF1 phosphorylation both by SRPK1 shRNA knockdown and by a selective inhibitor, SPHINX31, resulted in a switch in splicing to ∆Ex3PD1. Cholangiocarcinoma cell-mediated repression of T cell IL-2 expression was reversed by SPHINX31 (equivalent to pembrolizumab). CONCLUSIONS: These results indicate that switching of the splicing decision from flPD1 to ∆Ex3PD1 by targeting SRPK1 could represent a potential novel mechanism of immune checkpoint inhibition in cancer.

A Radiologist's Guide to the 2021 WHO Central Nervous System Tumor Classification: Part 2-Newly Described and Revised Tumor Types.

The fifth edition of the World Health Organization classification of tumors of the central nervous system (CNS), published in 2021, introduces major shifts in the classification of brain and spine tumors. These changes were necessitated by rapidly increasing knowledge of CNS tumor biology and therapies, much of which is based on molecular methods in tumor diagnosis. The growing complexity of CNS tumor genetics has required reorganization of tumor groups and acknowledgment of new tumor entities. For radiologists interpreting neuroimaging studies, proficiency with these updates is critical in providing excellent patient care. This review will focus on new or revised CNS tumor types and subtypes, beyond infiltrating glioma (described in part 1 of this series), with an emphasis on imaging features.

A clinical primer for the glymphatic system.

The complex and dynamic system of fluid flow through the perivascular and interstitial spaces of the CNS has new-found implications for neurological diseases. CSF movement throughout the CNS parenchyma is more dynamic than could be explained via passive diffusion mechanisms alone. Indeed, a semistructured glial-lymphatic (glymphatic) system of astrocyte-supported extracellular perivascular channels serves to directionally channel extracellular fluid, clearing metabolites and peptides to optimize neurological function. Clinical studies of the glymphatic network have to date proven challenging, with most data gleaned from rodent models and post-mortem investigations. However, increasing evidence suggests that disordered glymphatic function contributes to the pathophysiology of CNS ageing, neurodegenerative disease and CNS injuries, as well as normal pressure hydrocephalus. Unlocking such pathophysiology could provide important avenues towards novel therapeutics. We here provide a multidisciplinary overview of glymphatics and critically review accumulating evidence regarding its structure, function and hypothesized relevance to neurological disease. We highlight emerging technologies of relevance to the longitudinal evaluation of glymphatic function in health and disease. Finally, we discuss the translational opportunities and challenges of studying glymphatic science.

Perspectives on implementing Individual Placement and Support (IPS) within primary health care settings for adults living in British Columbia, Canada.

BACKGROUND: Individual placement and support (IPS) is an evidence-based practice (EBP) designed to help people with severe mental illness re-enter the labour market. Implementing an IPS program within a new context (e.g., primary health care setting) to support populations that are complex and multi-barriered presents a set of unique challenges and considerations. This paper provides community-based perspectives that identify implementation strengths and challenges and highlights potential strategies aimed at addressing emergent barriers. METHODS: A case study was conducted across three community health centres in British Columbia (BC), Canada, where a novel IPS program was embedded within primary care services. Data collection consisted of open-ended surveys and focus groups with service providers directly involved in program implementation and their associated clinical and managerial support teams (n = 15). Using the updated Consolidated Framework for Implementation Research (CFIR) as a guide, we performed deductive thematic analysis to identify key areas impacting IPS implementation. RESULTS: Integration with existing health care systems and primary health care teams and support from leadership across all levels were identified as both key facilitators and barriers to implementation. Facilitators and barriers were identified across all domains, with those within innovation and process most easily addressed. Four cross-cutting themes emerged for promoting more integrated and sustainable program implementation: investing in pre-implementation activities, supporting a dynamic and flexible program, building from community experiences, and developing a system for shared knowledge. CONCLUSIONS: Implementing an IPS program embedded within primary health care settings is complex and requires extensive planning and consultation with community-based service providers and decision-makers to achieve full integration. Future practice and policy decisions aimed at supporting employment and well-being should be made in collaboration with communities.

Interventional radiology in obstetric patients: A population-based record linkage study of use and outcomes.

INTRODUCTION: Interventional radiology (IR) is a technique for controlling hemorrhage and preserving fertility for women with serious obstetric conditions such as placenta accreta spectrum (PAS) or postpartum hemorrhage. This study examined maternal, pregnancy and hospital characteristics and outcomes for women receiving IR in pregnancy and postpartum. MATERIAL AND METHODS: A population-based record linkage study was conducted, including all women who gave birth in hospital in New South Wales or the major tertiary hospital in the neighboring Australian Capital Territory, Australia, between 2003 and 2019. Data were obtained from birth and hospital records. Characteristics and outcomes of women who underwent IR in pregnancy or postpartum are described. Outcomes following IR were compared in a high-risk cohort of women: those with PAS who had a planned cesarean with hysterectomy. Women were grouped by those who did and those who did did not have IR and were matched using propensity score and other factors. RESULTS: We identified IR in 236 pregnancies of 1 584 708 (15.0 per 100 000), including 208 in the delivery and 26 in a postpartum admission. Two-thirds of women receiving IR in the birth admission received a transfusion of red cells or blood products, 28% underwent hysterectomy and 12.5% were readmitted within 6 weeks. Other complications included: severe maternal morbidity (29.8%), genitourinary tract trauma/repair (17.3%) and deep vein thrombosis/pulmonary embolism (4.3%). Outcomes for women with PAS who underwent planned cesarean with hysterectomy were similar for those who did and did not receive IR, with a small reduction in transfusion requirement for those who received IR. CONCLUSIONS: Interventional radiology is infrequently used in pregnant women. In our study it was performed at a limited number of hospitals, largely tertiary centers, with the level of adverse outcomes reflecting use in a high-risk population. For women with PAS undergoing planned cesarean with hysterectomy, most outcomes were similar for those receiving IR and those not receiving IR, but IR may reduce bleeding.

That which is unseen: 3D printing for pediatric cerebrovascular education.

INTRODUCTION: Pediatric cerebrovascular lesions are very rare and include aneurysms, arteriovenous malformations (AVM), and vein of Galen malformations (VOGM). OBJECTIVE: To describe and disseminate a validated, reproducible set of 3D models for optimization of neurosurgical training with respect to pediatric cerebrovascular diseases METHODS: All pediatric cerebrovascular lesions treated at our institution with adequate imaging studies during the study period 2015-2020 were reviewed by the study team. Three major diagnostic groups were identified: aneurysm, AVM, and VOGM. For each group, a case deemed highly illustrative of the core diagnostic and therapeutic principles was selected by the lead and senior investigators for printing (CSG/JM). Files for model reproduction and free distribution were prepared for inclusion as Supplemental Materials. RESULTS: Representative cases included a 7-month-old female with a giant left MCA aneurysm; a 3-day-old male with a large, complex, high-flow, choroidal-type VOGM, supplied from bilateral thalamic, choroidal, and pericallosal perforators, with drainage into a large prosencephalic vein; and a 7-year-old male with a left frontal AVM with one feeding arterial vessel from the anterior cerebral artery and one single draining vein into the superior sagittal sinus CONCLUSION: Pediatric cerebrovascular lesions are representative of rare but important neurosurgical diseases that require creative approaches for training optimization. As these lesions are quite rare, 3D-printed models and open source educational materials may provide a meaningful avenue for impactful clinical teaching with respect to a wide swath of uncommon or unusual neurosurgical diseases.

Virtual surgical planning and mirrored, 3-dimensionally printed guides for corrective clavicle osteotomies in clavicle malunions and nonunions.

BACKGROUND: The objective of this study was to retrospectively review clinical and radiographic outcomes of patients who underwent corrective osteotomies for clavicle malunion and internal fixation for nonunion using a combination of virtual surgical planning, patient-specific 3-dimensional (3D)-printed clavicles, and 3D-printed cutting guides manufactured at the point of care. METHODS: Between 2015 and 2021, 18 patients underwent corrective osteotomy for a clavicle malunion (7 shoulders) or internal fixation for a clavicle nonunion (11 shoulders). There were 11 male and 7 female individuals with an average patient age of 43.9 (range 19-76) years. All patients underwent computed tomography evaluation of both clavicles. The DICOM files were manually segmented, virtual surgical planning was performed selectively using commercially available software, and a mirrored version of the normal clavicle was 3D printed along with a 3D-printed replica of the affected clavicle. Three-dimensionally printed mirrored clavicles were used in all cases to ensure adequate restoration of the shape and length of the clavicle and to precontour fixation plates. Virtual surgical planning and 3D-printed cutting guides for osteotomy were used in 4 of 18 (22%) patients. Either cancellous or structural intercalary bone grafting was used in 15 of 18 (83%) cases. Patients were contacted postoperatively to determine clinical outcome scores. Preoperative, early postoperative, and late postoperative radiographs were reviewed to assess for union and complications. The average follow-up time was 24.9 months. RESULTS: Radiographic evaluation at the most recent follow-up demonstrated adequate restoration of length and successful union for all shoulders. There were no complications or reoperations. Postoperative patient-reported outcomes could be obtained in 16 of 18 (88.9%) patients. At the most recent follow-up, the mean visual analog scale for pain was 2.38 points (range, 1-7), the mean shoulder American Shoulder and Elbow Surgeons score was 73.2 points (range, 25-100), and the mean Patient-Reported Outcome Measurement Information System Upper Extremity score was 26 points (range, 7-35). All (100%) the patients were satisfied with their outcome (9 very satisfied, 7 satisfied), and their mean subjective shoulder value was 73% (range, 10%-100%). However, 2 patients complained of hardware-related symptoms, and 1 patient had return of preoperative symptoms after an interim 2 years of pain relief. CONCLUSION: The use of mirrored 3D-printed clavicles combined with virtual surgical planning and patient-specific 3D guides provides a reliable technique for restoring native anatomy when performing corrective osteotomies for clavicle malunion or internal fixation for clavicle nonunion, with a high rate of satisfactory clinical and radiographic outcomes.

Asymptomatic bacteriuria in pregnancy.

BACKGROUND: Asymptomatic bacteriuria (ASB) is associated with adverse maternal and neonatal outcomes and is routinely screened for and treated in the first trimester. Prevalence of ASB in the second and third trimesters of pregnancy is unknown. AIMS: The aim is to determine the prevalence of ASB in the second and third trimesters of pregnancy. METHODS: Prospective cohort study of 150 pregnant women. Mid-stream urine samples were tested for ASB in the second (24-28+6 ) and third (32-36+6 ) trimesters. Women were assigned to one of two groups: (i) ASB in any trimester of pregnancy and (ii) no evidence of ASB in pregnancy. Maternal and neonatal outcomes were compared between groups. RESULTS: Among 143 women included in the study, the rate of ASB was 4.9% (2.1, 2.1 and 3.2% in the first, second and third trimesters, respectively). Of those with ASB, 14% had it in every trimester, whereas 43% had it on two or more samples. Of those with ASB in pregnancy, 43% were detected for the first time in the third trimester. Rates of maternal and neonatal outcomes were not statistically significantly different between the two groups. No women with ASB were induced for chorioamnionitis or growth restriction. CONCLUSION: The rate of ASB was highest in the third trimester of pregnancy, with rates of 2.1, 2.1 and 3.2% in the first, second and third trimesters, respectively. This study was underpowered to assess maternal and fetal outcomes. Although numbers were small, the absence of ASB in the first trimester was a poor predictor of ASB in the third trimester.

Trends in early gestation stillbirths and neonatal deaths in New South Wales, Australia 2002-2019.

BACKGROUND: Little research has focused on understanding trends in early gestation (20-27 weeks) stillbirths and neonatal deaths. AIMS: To examine trends in early gestation stillbirths and neonatal deaths in New South Wales (NSW), Australia. MATERIALS AND METHODS: Population-based cohort study of all births ≥20 weeks gestation among female NSW residents during 2002 to 2019, induced pregnancy terminations excluded. Stillbirth rates by gestational age and birth year were calculated per 1000 fetuses-at-risk (FAR). Neonatal death rates by gestational age and birth year were calculated per 1000 live births. Linear regression was used to examine trends in stillbirth and neonatal death rates among all, singleton and twin births. RESULTS: Declining trends in early gestation stillbirth and neonatal death rates were found. Stillbirth rates decreased from 1.9 and 0.9/1000 FAR in 2002 to 1.6 and 0.7 in 2019 for 20-23 and 24-27 week groups, respectively. Neonatal rates decreased from 940 and 315/1000 live births in 2002 to 925 and 189 in 2019 for the 20-23 and 24-27 week groups, respectively. Among singleton births, declining trends in stillbirth and neonatal death rates across all age groups were observed, except for 37-38 week stillbirths. No trends in twin stillbirth rates were found across gestational age groups, although a decreasing trend was observed for 20-23 week twin neonatal deaths. CONCLUSIONS: Trends in early gestation stillbirth and neonatal deaths have declined in recent decades in NSW but further efforts are needed to reduce both early and late gestation stillbirth rates among twin births.

Craniomaxillofacial Trauma: The Past, Present and the Future.

Reconstruction of facial trauma has seen a significant evolutionary leap in the last 100 years. The current surgical management of facial fractures was made possible by the efforts and creativity of pioneer surgeons, advances in anatomic understanding, and the continued development of biomaterials and imaging technologies. Virtual surgical planning (VSP) and 3-dimensional printing (3DP) are being incorporated into the management of acute facial trauma. The integration of this technology at the point of care is rapidly expanding globally. This article reviews the history of the management of craniomaxillofacial trauma, current practices, and future directions. The use of VSP and 3DP in facial trauma care is highlighted with a description of EPPOCRATIS, a rapid point-of-care process incorporating VSP and 3DP at the trauma center.

Fabrication of custom oral positioning devices in head and neck proton radiotherapy.

With complex head and neck diseases that closely approximate crucial organs or have advanced spread and cannot be surgically resected, intensity modulated proton beam radiotherapy is favored due to its superior dose targeting through magnetic manipulation of the proton energy. A radiation mask and an oral positioning device immobilize craniofacial, cervical, and oral structures for accurate and reliable radiation delivery. Widely available prefabricated thermoplastic oral positioning devices are manufactured in standardized forms and materials that unpredictably affect the proton beams' pathways and range. This technique article showcases a workflow that combines analog and digital dental techniques to produce a customized 3D-printed oral positioning device within 2 appointments.