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Summary of Background Data: Iatrogenic injury of the vertebral artery (VA) in the context of surgical approaches to the cervical spine has been cited as a relatively rare complication with varying degrees of severity ranging from minimal injury to acute stroke and can result in death. It is estimated that ~50% of cases of iatrogenic VA injury are preventable after postoperatively examining a patient's preoperative imaging. Despite the low incidence (<2%) of this complication, the potential associated morbidity demonstrates the importance of meticulous preoperative vascular consideration., Objective: This study aims to emphasize the importance of preoperative vascular screening during anterior cervical access planning visualized through a rare case of a VA aberration in a 47-year-old patient., Study Design: This study is designed as a retrospective case report., Methods: A thorough chart review was performed for this subject including all prior medical records, imaging studies, imaging reports, operative notes, and communication records., Results: The subject was found to have a history of patent foramen ovale (PFO) repair with a rare vertebral artery malformation described as a medial transposition of the vertebral artery out of the vertebral artery foramen between C3 and C4., Conclusions: Consideration of cervical anatomy, particularly the VA, is key to minimizing the risk of adverse surgical outcomes in both anterior and posterior approaches to the cervical spine. During the workup process, the patient's primary care providers, radiologists, and surgeons should be aware of the potential variations of the VA with particular attention given to the course of the VA on MR imaging., Level of Evidence: Level IV., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

We conducted an epidemiological study by using the National Electronic Injury Surveillance System (NEISS) database to assess and quantify waterskiing injuries between 2012 and 2022. A total of 898 injuries were reported, primarily among Caucasian males during competition. Head (177, 20%), face (93, 10%), and knee (70, 8%) were the most prevalent types of injuries. Common physical examination findings included muscle strains, ligament sprains, lacerations, and fractures. Although rare, there were reported cases of dental injury, hemorrhage, crushing, foreign body, and amputation as well. These findings suggest that protective equipment, particularly headgear, is necessary to reduce the incidence of waterskiing injuries., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Muir et al.)

The meniscus of the knee serves as a crucial load-bearing structure, and its damage can significantly impact weight distribution. In addressing focal meniscal defects, segmental meniscal allograft transplantation (SMALT) emerges as an innovative solution. Here, we detail a case involving a young, active female who underwent SMALT augmented with osteochondral allograft transplantation (OCA) and bone marrow aspirate concentration (BMAC). The patient, a 40-year-old former Division I volleyball player, previously underwent arthroscopic procedures and presented with knee pain alongside complex lateral meniscus tear evident in magnetic resonance imaging (MRI) findings. Initial arthroscopy revealed multiple tears, including segmental deficiency at the posterior horn-body junction and a horizontal cleavage tear. Despite failed attempts at repair due to the meniscal gap, a second-stage lateral SMALT was performed, with the allograft soaked in the patient's BMAC, supplemented with OCA to the lateral femoral condyle. Rehabilitation protocols tailored to both SMALT and OCA were implemented. This represents the first documented instance of lateral SMALT, extending the scope of viable solutions for segmental meniscal deficiencies, and marking a significant milestone in orthopedic practice., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Muir et al.)

Anterior cruciate ligament tears are primarily treated by reconstruction. The development of novel surgical techniques has led to the reconsideration of this approach. Additionally, Grade III tibial-sided medial collateral ligament tears should be treated surgically due to decreased blood flow and poor healing. We describe the surgical repair of a Grade III tibial-sided tear with partial femoral avulsion of the medial collateral ligament and tear of the posterolateral bundle of the anterior cruciate ligament in a competitive high school athlete. A 17-year-old male presented to the Sports Medicine Clinic after injuring his left knee in a football game. Radiographs suggested normal skeletal anatomical alignment with no acute fractures. Magnetic resonance imaging identified a partial injury of the femoral attachment of the medial collateral ligament and a Grade III medial collateral ligament tear where it attached to the tibia. Arthroscopic evaluation of the knee revealed a posterolateral anterior cruciate ligament tear. Operative management included surgical repair of the Grade III tibial-sided medial collateral ligament tear and the posterolateral anterior cruciate ligament tear. Operative repair of medial collateral ligament and anterior cruciate ligament tears provides an alternative approach to the management of surgical reconstruction., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Muir et al.)

Ulcerative colitis is a chronic inflammatory bowel disease that results in continuous colon inflammation. It is uncommonly diagnosed during pregnancy, and if quiescent before pregnancy, becomes active very rarely. Current literature has found that amelioration of the disease can be common during the second and third trimesters. However, if ulcerative colitis is active, it has the potential to result in premature delivery and low birth weight. This case focuses on a rare presentation of primary ulcerative colitis diagnosed in a 22-year-old multiparous patient to highlight the importance of a comprehensive differential diagnosis in pregnant patients with seemingly benign symptomatology., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Rodriguez et al.)

Traumatic brain injury (TBI) is one of the most common causes of morbidity and mortality worldwide. Severe TBI carries the greatest risk of brain death progression. There are currently no laboratory markers that predict patient's outcome. We hypothesize that the degree of hypophosphatemia (HP) in TBI is an indicator for progression to brain death. A total of 336 patients, ages 15-89, with a GCS of 8 or less at admission were identified and retrospectively analyzed. Demographics, laboratory studies, and brain death (BD) were collected. Univariate analysis demonstrated HP was correlated with BD ( P < .0002). Multivariate analysis showed that phosphate was the only measured electrolyte correlated to BD with a P value < .0001. Mechanism of hypophosphatemia may be related to BD progression and provide future areas for study.

Vitamin K is a micronutrient necessary for γ-carboxylation of glutamic acids. This post-translational modification occurs in the endoplasmic reticulum (ER) and affects secreted proteins. Recent clinical studies implicate vitamin K in the pathophysiology of diabetes, but the underlying molecular mechanism remains unknown. Here, we show that mouse β cells lacking γ-carboxylation fail to adapt their insulin secretion in the context of age-related insulin resistance or diet-induced β cell stress. In human islets, γ-carboxylase expression positively correlates with improved insulin secretion in response to glucose. We identify endoplasmic reticulum Gla protein (ERGP) as a γ-carboxylated ER-resident Ca 2+ -binding protein expressed in β cells. Mechanistically, γ-carboxylation of ERGP protects cells against Ca 2+ overfilling by diminishing STIM1 and Orai1 interaction and restraining store-operated Ca 2+ entry. These results reveal a critical role of vitamin K-dependent carboxylation in regulation of Ca 2+ flux in β cells and in their capacity to adapt to metabolic stress., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Genomic sequencing can generate complex results, including variants of uncertain significance (VUS). In general, VUS should not inform clinical decision-making. This study aimed to assess the public's expected management of VUS., Methods: An online, hypothetical survey was conducted among members of the Canadian public preceded by an educational video. Participants were randomized to 1 of 2 arms, VUS or pathogenic variant in a colorectal cancer gene, and asked which types of health services they expected to use for this result. Expected health service use was compared between randomization arms, and associations between participants' sociodemographic characteristics, attitudes, and medical history were explored., Results: Among 1003 respondents (completion rate 60%), more participants expected to use each type of health service for a pathogenic variant than for a VUS. However, a considerable proportion of participants expected to request monitoring (73.4%) and consult health care providers (60.9%) for a VUS. There was evidence to support associations between expectation to use health services for a VUS with family history of genetic disease, family history of cancer, education, and attitudes toward health care and technology., Conclusion: Many participants expected to use health services for a VUS in a colorectal cancer predisposition gene, suggesting a potential disconnect between patients' expectations for VUS management and guideline-recommended care., Competing Interests: Conflict of Interest The authors declare no conflicts of interest., (Copyright © 2023 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)

The primary function of the umbilical cord is to transport blood to and from the fetus. It carries deoxygenated blood away from the fetus by two umbilical arteries, and oxygenated blood from the placenta toward the fetus by an umbilical vein. In some cases, the umbilical cord can form a true knot increasing the risk of asphyxia and fetal demise. The umbilical cord may also form a false knot, which is only a kink and will not increase fetal risk of abnormalities. A 40-year-old woman, gravida six, parity three (G6P3), presented to the hospital in active labor after 39.1 weeks of gestation. Six hours after admission a healthy male fetus was delivered with one nuchal cord. The placenta was delivered approximately 3 minutes later. Upon inspection, the presence of a double and a single true knot of the umbilical cord was noted. This case describes a fetus with a double and single true knot of the umbilical cord that was not apparent by ultrasonography., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Waldron et al.)

Expanded genetic testing guidelines for hereditary cancers, increased utilization of large multigene panels, and improved methods for reclassifying variants have led to a greater need to understand how variant reclassification and patient re-contact are managed. This study aimed to describe the process of variant reclassification and subsequent patient re-contact at a comprehensive cancer genetic counseling service in a large metropolitan medical center with several statewide satellite locations. A retrospective chart review was performed to identify reclassified variants between 1/1/1997 and 12/1/2020. In total, 8.4% (211/2503) of variants were reclassified over the 24-year period, which includes multiple cases involving the same unique variant. Several variants underwent more than one reclassification, resulting in 232 total reclassifications among 194 individuals. Nearly all reclassifications were prompted by the laboratory (99.1%; 230/232) rather than the genetics clinic staff. Overall, 10.3% (24/232) of all reclassifications were upgrades, but only 9.1% (21/232) led to a change in management recommendations. The median time for variant reclassification was 1.7 years (interquartile range [IQR] = 0.8-3.2 years). There was no statistically significant difference in the time to reclassification for White patients (median = 1.6 years; IQR = 0.8-2.8 years) compared to non-White patients (median = 2.0 years; IQR = 0.9-3.7 years; Mann-Whitney U = 4,764.0, p = 0.066). Patient re-contact was attempted for 97.4% (226/232) of variants and was always performed by a genetic counselor, most often through a mailed letter (85.8%, 194/226). Specifically for reclassifications that led to a change in management recommendations, re-contact was always attempted, most often through combined telephone and mailed letter (95.2%; 20/21). Overall, the median time from reclassification to attempted patient re-contact was 13 days (range: 0-589 days). The characterization of this clinic's reclassification and re-contact procedures can serve as an example for other genetics clinics trying to incorporate re-contact into their workflow., (© 2022 National Society of Genetic Counselors.)

Variants of uncertain significance (VUS) are frequently reclassified but recontacting patients with updated results poses significant resource challenges. We aimed to characterize public and patient preferences for being recontacted with updated results. A discrete choice experiment (DCE) was administered to representative samples of the Canadian public and cancer patients. DCE attributes were uncertainty, cost, recontact modality, choice of results, and actionability. DCE data were analyzed using a mixed logit model and by calculating willingness to pay (WTP) for types of recontact. Qualitative interviews exploring recontact preferences were analyzed thematically. DCE response rate was 60% (n = 1003, 50% cancer patient participants). 31 participants were interviewed (11 cancer patients). Interviews revealed that participants expected to be recontacted. Quantitatively, preferences for how to be recontacted varied based on certainty of results. For certain results, WTP was highest for being recontacted by a doctor with updates ($1075, 95% CI: $845, $1305) and for contacting a doctor to request updates ($1038, 95% CI: $820, $1256). For VUS results, WTP was highest for an online database ($1735, 95% CI: $1224, $2247) and for contacting a doctor ($1705, 95% CI: $1102, $2307). Qualitative data revealed that preferences for provider-mediated recontact were influenced by trust in healthcare providers. Preferences for a database were influenced by lack of trust in providers and desire for control. Patients and public participants support an online database (e.g. patient portal) to recontact for VUS, improving feasibility, and provider-mediated recontact for certain results, consistent with usual care., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The field of regenerative medicine is developing technologies that, in the near future, will offer alternative approaches to either cure diseases affecting the gastrointestinal tract or slow their progression by leveraging the intrinsic ability of our tissues and organs to repair after damage. This article will succinctly illustrate the three technologies that are closer to clinical translation-namely, human intestinal organoids, sphincter bioengineering and decellularization, whereby the cellular compartment of a given segment of the digestive tract is removed to obtain a scaffold consisting of the extracellular matrix. The latter will be used as a template for the regeneration of a functional organ, whereby the newly generated cellular compartment will be obtained from the patient's own cells. Although clinical application of this technology is approaching, product development challenges are being tackled to warrant safety and efficacy., (Copyright © 2021 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Islet transplantation (ITx) has the potential to become the standard of care in beta cell replacement medicine but its results remain inferior to those obtained with whole pancreas transplantation. The protocols currently used for human islet isolation are under scrutiny because they are based on the enzymatic digestion of the organ, whereby the pancreas is demolished, its connections to the body are lost and islets are irreversibly damaged. Islet damage is characterized by critical factors such as the destruction of the extracellular matrix (ECM), which represents the 3D framework of the islet niche and whose loss is incompatible with islet euphysiology. Researchers are proposing the use of ECM-based scaffolds derived from the mammalian pancreas to address this problem and ultimately improve islet viability, function, and lifespan. Currently available methods to obtain such scaffolds are harsh because they are largely detergent based. Thus, we propose a new, detergent-free method that creates less ECM damage and can preserve critical components of pancreatic ECM. The results show that the newly developed decellularization protocol allowed the achievement of complete DNA clearance while the ECM components were retained. The ECM obtained was tested for cytotoxicity and encapsulated with human pancreatic islets which showed a positive cellular behavior with insulin secretion when stimulated with glucose challenge. Collectively, we propose a new method for the decellularization of the human pancreas without the use of conventional ionic and non-ionic chemical detergents. This protocol and the ECM obtained with it could be of use for both in vitro and in vivo applications.

Purpose: To evaluate the effectiveness of the Genomics ADvISER (www.genomicsadviser.com) decision aid (DA) for selection of secondary findings (SF), compared with genetic counseling alone., Methods: A randomized controlled trial (RCT) was conducted to evaluate whether the Genomics ADvISER is superior to genetic counseling when hypothetically selecting SF. Participants were randomized to use the DA followed by discussion with a genetic counselor, or to genetic counseling alone. Surveys were administered at baseline and post-intervention. Primary outcome was decisional conflict. Secondary outcomes were knowledge, preparation for, and satisfaction with decision-making, anxiety, and length of counseling session., Results: Participants (n = 133) were predominantly White/European (74%), female (90%), and ≥50 years old (60%). Decisional conflict (mean difference 0.05; P = 0.60), preparation for decision-making (0.17; P = 0.95), satisfaction with decision (-2.18; P = 0.06), anxiety (0.72; P = 0.56), and knowledge of sequencing limitations (0.14; P = 0.70) did not significantly differ between groups. However, intervention participants had significantly higher knowledge of SF (0.39; P < 0.001) and sequencing benefits (0.97; P = 0.01), and significantly shorter counseling time (24.40 minutes less; P < 0.001) CONCLUSIONS: The Genomics ADvISER did not decrease decisional conflict but reduced counseling time and improved knowledge. This decision aid could serve as an educational tool, reducing in-clinic time and potentially health care costs.

Evolutionary adaptation to extreme environments often requires coordinated changes in multiple intersecting physiological pathways, but how such multi-trait adaptation occurs remains unresolved. Transcription factors, which regulate the expression of many genes and can simultaneously alter multiple phenotypes, may be common targets of selection if the benefits of induced changes outweigh the costs of negative pleiotropic effects. We combined complimentary population genetic analyses and physiological experiments in North American deer mice (Peromyscus maniculatus) to examine links between genetic variation in transcription factors that coordinate physiological responses to hypoxia (hypoxia-inducible factors, HIFs) and multiple physiological traits that potentially contribute to high-altitude adaptation. First, we sequenced the exomes of 100 mice sampled from different elevations and discovered that several SNPs in the gene Epas1, which encodes the oxygen sensitive subunit of HIF-2α, exhibited extreme allele frequency differences between highland and lowland populations. Broader geographic sampling confirmed that Epas1 genotype varied predictably with altitude throughout the western US. We then discovered that Epas1 genotype influences heart rate in hypoxia, and the transcriptomic responses to hypoxia (including HIF targets and genes involved in catecholamine signaling) in the heart and adrenal gland. Finally, we used a demographically-informed selection scan to show that Epas1 variants have experienced a history of spatially varying selection, suggesting that differences in cardiovascular function and gene regulation contribute to high-altitude adaptation. Our results suggest a mechanism by which Epas1 may aid long-term survival of high-altitude deer mice and provide general insights into the role that highly pleiotropic transcription factors may play in the process of environmental adaptation., Competing Interests: The authors have declared that no competing interests exist.

Purpose of Review: The current review summarizes contemporary decellularization and hydrogel manufacturing strategies in the field of tissue engineering and regenerative medicine., Recent Findings: Decellularized extracellular matrix (ECM) bioscaffolds are a valuable biomaterial that can be purposed into various forms of synthetic tissues such as hydrogels. ECM-based hydrogels can be of animal or human origin. The use of human tissues as a source for ECM hydrogels in the clinical setting is still in its infancy and current literature is scant and anecdotal, resulting in inconclusive results., Summary: Thus far the methods used to obtain hydrogels from human tissues remains a work in progress. Gelation, the most complex technique in obtaining hydrogels, is challenging due to remarkable heterogeneity of the tissues secondary to interindividual variability. Age, sex, ethnicity, and preexisting conditions are factors that dramatically undermine the technical feasibility of the gelation process. This is contrasted with animals whose well defined anatomical and histological characteristics have been selectively bred for the goal of manufacturing hydrogels.

Background: Currently, platelet-poor plasma (PPP) is a discarded waste product of platelet-rich plasma (PRP) and may contain valuable proteins., Purpose/hypothesis: The study's goal was to evaluate the concentration of plasma as a potential additive biotherapy for the treatment of osteoarthritis. We hypothesized that a novel polyacrylamide concentration device would efficiently concentrate insulin-like growth factor-1 (IGF-1) from PPP and be additive to PRP or autologous protein solution (APS)., Study Design: Descriptive laboratory study., Methods: A laboratory study was conducted with human and equine whole blood from healthy volunteers/donors. Fresh samples of blood and plasma were processed and characterized for platelet, white blood cell, and growth factor/cytokine content and then quantified by enzyme-linked immunosorbent assays specific for IGF-1, transforming growth factor-β, interleukin-1β, and interleukin-1 receptor antagonist as representatives of cartilage anabolic and inflammatory mediators., Results: A potent cartilage anabolic protein, IGF-1, was significantly concentrated by the polyacrylamide concentration device in both human and equine PPP. The polyacrylamide device also substantially increased plasma proteins over whole blood, most dramatically key proteins relevant to the treatment of osteoarthritis, including transforming growth factor-β (29-fold over blood) and interleukin-1 receptor antagonist (70-fold over plasma)., Conclusion: Concentrated PPP is a unique source for biologically relevant concentrations of IGF-1. PRP and APS can produce greater concentrations of other anabolic and anti-inflammatory proteins not found in plasma., Clinical Relevance: The polyacrylamide device efficiently concentrated PPP to create a unique source of IGF-1 that may supplement orthopaedic biologic therapies.

There is an increasing focus on the relative cost-effectiveness and sustainability of delivering high-quality cancer care, with most emphasis, debatably, given to cost control of innovative treatments. It is difficult to calculate all the direct and indirect contributors to the total cost of cancer treatment, but it is estimated that cancer drugs constitute 10% to 30% of the total cost of cancer care. A 2007 study in France showed the contribution of drug costs was less than 20%, with approximately 70% of the total expenditure on cancer accounted for by health care resource use, such as hospitalization. The U.K. government established the National Institute for Health and Care Excellence (NICE)-the dominant function of which is technology appraisal-to assess the clinical and cost-effectiveness of new pharmaceutical and biopharmaceutical products. This is to ensure that all National Health Service (NHS) patients have equitable access to the most clinically effective and cost-effective treatments that are viable. NICE has developed a transparent, public process to judge incremental cost-effectiveness using the quality-adjusted life year (QALY), which allows comparisons of cost-effectiveness across medical specialties. NICE has been both lauded and criticized-especially when it passes judgment on marginally effective but expensive anticancer drugs-but it provides a route to "rational rationing" and, therefore, may contribute to sustainable cancer care by highlighting the issue of affordable medicine. This implies a challenge to the wider oncology community as to how we might cooperate to introduce the concept of value-driven cancer care.

The yawning gap between what we know and what we do has major implications for patients. By putting into practice what we know now, we will have a bigger impact on the health of individuals and populations than any drug or technology discovered in the new decade. The assumption underlying this article is that the gap can be closed by thinking, planning, analyzing, mobilizing,managing, personalizing, and using knowledge. There is, however,a risk that the attempted solution may perpetuate or aggravate the problem, and surgeons must be aware of the dangers of substituting thought for action, when knowledge management becomes an industry of its own, remote from the core activities of the organization and those who deliver them.