Osteoarthritis Increases the Frequency and Duration of Postoperative Hand Clinic Visits after Carpal Tunnel Release.

Background: Carpal tunnel syndrome affects up to 6% of the general population, and surgical intervention is often required to ameliorate symptoms. Osteoarthritis (OA) is a common condition that often coexists with carpal tunnel syndrome. We hypothesized that patients with preexisting OA use more healthcare resources after carpal tunnel release (CTR) than patients without arthritis. Methods: This was a retrospective cohort study at a single academic center between January 1, 2018 and November 1, 2021. Patients who underwent CTR were included. Preoperative carpal tunnel symptoms, diagnostic tests, medications, and concomitant OA were abstracted. Hand, wrist, and basal joint arthritis were specified. The primary outcome was healthcare utilization represented by duration and frequency of hand clinic and occupational therapy (OT) follow-up. In total, 312 hands were included. Multivariable analysis was performed. Results: The average duration of hand clinic follow-up among patients without arthritis was 25.3 days compared with 87.1 days for patients with any arthritis (P = 0.0375) and 172 days for patients with wrist arthritis (P = 0.012). The average number of postoperative surgeon visits was increased in patients with hand arthritis, with an average of 2.3 visits versus 1.34 visits for patients without arthritis (P = 0.003). Both the number of OT visits and the duration of OT follow-up did not differ between cohorts. Conclusion: After CTR, patients with preexisting OA use more healthcare resources than patients without OA.

"The Impact of Neighborhood and Socioeconomic Disparities on Distal Radius Fracture Follow-Up Adherence: A Retrospective Cohort Study".

BACKGROUND: The aims of this retrospective cohort study were to assess if the Area Deprivation Index (ADI), a novel neighborhood-level socioeconomic disparities metric, is associated with follow-up non-adherence, and secondarily, determine the individual-level socioeconomic factors associated with follow-up non-adherence after treatment of distal radius fractures (DRF). METHODS: We included all patients who underwent non-operative and operative management of DRF at an academic level I trauma center between 2019 and 2021. A manual chart review was performed to collect data on ADI, sociodemographic factors, injury characteristics, conservative and surgical interventions, and healthcare utilization. RESULTS: There was a significant, weak negative Spearman-ranked correlation between ADI state deciles and clinic attendance rates (rs(220) = -.144; [95% CI: -.274, -.009] p = .032). Socioeconomic factors associated with significant differences in clinic attendance rates were having a spouse or partner (protective) (p = .007), Medicaid insurance (p = .013), male sex (p = .023), and current smokers (p = .026). Factors associated with differences in no show rates were having spouse or partner (OR .326; [95% CI: .123 - .867] p = .025), Medicaid insurance (OR 7.78; [95% CI: 2.15 - 28.2] p = .002), male sex (OR 4.09; [95% CI: 1.72 - 9.74] p = .001), and cigarette use (OR 5.07; [95% CI: 1.65 - 15.6] p = .005). CONCLUSIONS: ADI has a weak, negative correlation with clinic attendance rates following DRF treatment. Significant disparities in clinic follow-up adherence exist between patients with different marital status, insurances, sexes, and cigarette use.

Insurance Status Predicts Hand Therapy Adherence Following Flexor Tendon Repair: A Retrospective Cohort Study".

BACKGROUND: Many patients are not adherent to hand therapy rehabilitation following surgical repair of traumatic flexor tendon injuries, which can negatively affect surgical outcomes and long-term hand function. We aimed to identify the factors that predict patient non-adherence to hand therapy following flexor tendon repair surgery. METHODS: This retrospective cohort study included 154 patients who underwent surgical repair of flexor tendon injuries at a level I trauma center between January 2015 and January 2020. A manual chart review was performed to collect demographic data, insurance status, injury characteristics, and details of the postoperative course including health care utilization. RESULTS: Factors significantly associated with occupational therapy no-shows included Medicaid insurance (OR, 8.35; 95% CI, 2.91 to 24.0; p < 0.001), self-identified Black race (OR, 7.28; 95% CI, 1.78 to 29.7; p = 0.006), and current cigarette smoker status (OR, 2.69; 95% CI, 1.18 to 6.15; p = 0.019). Patients without insurance attended 73.8% of their OT visits and patients with Medicaid attended 72.0% of their visits, which were significantly lower rates than those with private insurance 90.7% (p=0.026 and p=0.001, respectively). Patients with Medicaid were 8 times more likely to seek emergency department care postoperatively than patients with private insurance (p=0.002). CONCLUSIONS: Significant disparities in hand therapy adherence following flexor tendon repair surgery exist between patients with different insurance statuses, races, and tobacco use. Understanding these disparities can help providers identify at-risk patients to improve hand therapy utilization and postoperative outcomes.

Frem1 activity is regulated by Sonic hedgehog signaling in the cranial neural crest mesenchyme during midfacial morphogenesis.

BACKGROUND: Frem1 has been linked to human face shape variation, dysmorphology, and malformation, but little is known about its regulation and biological role in facial development. RESULTS: During midfacial morphogenesis in mice, we observed Frem1 expression in the embryonic growth centers that form the median upper lip, nose, and palate. Expansive spatial gradients of Frem1 expression in the cranial neural crest cell (cNCC) mesenchyme of these tissues suggested transcriptional regulation by a secreted morphogen. Accordingly, Frem1 expression paralleled that of the conserved Sonic Hedgehog (Shh) target gene Gli1 in the cNCC mesenchyme. Suggesting direct transcriptional regulation by Shh signaling, we found that Frem1 expression is induced by SHH ligand stimulation or downstream pathway activation in cNCCs and observed GLI transcription factor binding at the Frem1 transcriptional start site during midfacial morphogenesis. Finally, we found that FREM1 is sufficient to induce cNCC proliferation in a concentration-dependent manner and that Shh pathway antagonism reduces Frem1 expression during pathogenesis of midfacial hypoplasia. CONCLUSIONS: By demonstrating that the Shh signaling pathway regulates Frem1 expression in cNCCs, these findings provide novel insight into the mechanisms underlying variation in midfacial morphogenesis.

Initial evaluation of a mobile SARS-CoV-2 RT-LAMP testing strategy.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) control in the United States remains hampered, in part, by testing limitations. We evaluated a simple, outdoor, mobile, colorimetric reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay workflow where self-collected saliva is tested for SARS-CoV-2 RNA. From July 16 to November 19, 2020, 4,704 surveillance samples were collected from volunteers and tested for SARS-CoV-2 at 5 sites. A total of 21 samples tested positive for SARS-CoV-2 by RT-LAMP; 12 were confirmed positive by subsequent quantitative reverse-transcription polymerase chain reaction (qRT-PCR) testing, while 8 were negative for SARS-CoV-2 RNA, and 1 could not be confirmed because the donor did not consent to further molecular testing. We estimated the RT-LAMP assay's false-negative rate from July 16 to September 17, 2020 by pooling residual heat-inactivated saliva that was unambiguously negative by RT-LAMP into groups of 6 or less and testing for SARS-CoV-2 RNA by qRT-PCR. We observed a 98.8% concordance between the RT-LAMP and qRT-PCR assays, with only 5 of 421 RT-LAMP negative pools (2,493 samples) testing positive in the more sensitive qRT-PCR assay. Overall, we demonstrate a rapid testing method that can be implemented outside the traditional laboratory setting by individuals with basic molecular biology skills and can effectively identify asymptomatic individuals who would not typically meet the criteria for symptom-based testing modalities.

Initial Evaluation of a Mobile SARS-CoV-2 RT-LAMP Testing Strategy.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) control in the United States remains hampered, in part, by testing limitations. We evaluated a simple, outdoor, mobile, colorimetric reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assay workflow where self-collected saliva is tested for SARS-CoV-2 RNA. From July 16, 2020, to November 19, 2020, surveillance samples (n = 4704) were collected from volunteers and tested for SARS-CoV-2 at 5 sites. Twenty-one samples tested positive for SARS-CoV-2 by RT-LAMP; 12 were confirmed positive by subsequent quantitative reverse-transcription polymerase chain reaction (qRT-PCR) testing, whereas 8 tested negative for SARS-CoV-2 RNA, and 1 could not be confirmed because the donor did not consent to further molecular testing. We estimated the false-negative rate of the RT-LAMP assay only from July 16, 2020, to September 17, 2020 by pooling residual heat-inactivated saliva that was unambiguously negative by RT-LAMP into groups of 6 or fewer and testing for SARS-CoV-2 RNA by qRT-PCR. We observed a 98.8% concordance between the RT-LAMP and qRT-PCR assays, with only 5 of 421 RT-LAMP-negative pools (2493 total samples) testing positive in the more-sensitive qRT-PCR assay. Overall, we demonstrate a rapid testing method that can be implemented outside the traditional laboratory setting by individuals with basic molecular biology skills and that can effectively identify asymptomatic individuals who would not typically meet the criteria for symptom-based testing modalities.

Loop-Mediated Isothermal Amplification Detection of SARS-CoV-2 and Myriad Other Applications.

As the second year of the COVID-19 pandemic begins, it remains clear that a massive increase in the ability to test for SARS-CoV-2 infections in a myriad of settings is critical to controlling the pandemic and to preparing for future outbreaks. The current gold standard for molecular diagnostics is the polymerase chain reaction (PCR), but the extraordinary and unmet demand for testing in a variety of environments means that both complementary and supplementary testing solutions are still needed. This review highlights the role that loop-mediated isothermal amplification (LAMP) has had in filling this global testing need, providing a faster and easier means of testing, and what it can do for future applications, pathogens, and the preparation for future outbreaks. This review describes the current state of the art for research of LAMP-based SARS-CoV-2 testing, as well as its implications for other pathogens and testing. The authors represent the global LAMP (gLAMP) Consortium, an international research collective, which has regularly met to share their experiences on LAMP deployment and best practices; sections are devoted to all aspects of LAMP testing, including preanalytic sample processing, target amplification, and amplicon detection, then the hardware and software required for deployment are discussed, and finally, a summary of the current regulatory landscape is provided. Included as well are a series of first-person accounts of LAMP method development and deployment. The final discussion section provides the reader with a distillation of the most validated testing methods and their paths to implementation. This review also aims to provide practical information and insight for a range of audiences: for a research audience, to help accelerate research through sharing of best practices; for an implementation audience, to help get testing up and running quickly; and for a public health, clinical, and policy audience, to help convey the breadth of the effect that LAMP methods have to offer.

Developmental Toxicity Assessment of Piperonyl Butoxide Exposure Targeting Sonic Hedgehog Signaling and Forebrain and Face Morphogenesis in the Mouse: An in Vitro and in Vivo Study.

BACKGROUND: Piperonyl butoxide (PBO) is a pesticide synergist used in residential, commercial, and agricultural settings. PBO was recently found to inhibit Sonic hedgehog (Shh) signaling, a key developmental regulatory pathway. Disruption of Shh signaling is linked to birth defects, including holoprosencephaly (HPE), a malformation of the forebrain and face thought to result from complex gene-environment interactions. OBJECTIVES: The impact of PBO on Shh signaling in vitro and forebrain and face development in vivo was examined. METHODS: The influence of PBO on Shh pathway transduction was assayed in mouse and human cell lines. To examine its teratogenic potential, a single dose of PBO (22-1,800mg/kg) was administered by oral gavage to C57BL/6J mice at gestational day 7.75, targeting the critical period for HPE. Gene-environment interactions were investigated using Shh+/- mice, which model human HPE-associated genetic mutations. RESULTS: PBO attenuated Shh signaling in vitro through a mechanism similar to that of the known teratogen cyclopamine. In utero PBO exposure caused characteristic HPE facial dysmorphology including dose-dependent midface hypoplasia and hypotelorism, with a lowest observable effect level of 67mg/kg. Median forebrain deficiency characteristic of HPE was observed in severely affected animals, whereas all effective doses disrupted development of Shh-dependent transient forebrain structures that generate cortical interneurons. Normally silent heterozygous Shh null mutations exacerbated PBO teratogenicity at all doses tested, including 33mg/kg. DISCUSSION: These findings demonstrate that prenatal PBO exposure can cause overt forebrain and face malformations or neurodevelopmental disruptions with subtle or no craniofacial dysmorphology in mice. By targeting Shh signaling as a sensitive mechanism of action and examining gene-environment interactions, this study defined a lowest observable effect level for PBO developmental toxicity in mice more than 30-fold lower than previously recognized. Human exposure to PBO and its potential contribution to etiologically complex birth defects should be rigorously examined. https://doi.org/10.1289/EHP5260.

Spontaneous subclavian artery dissection: a pain in the neck diagnosis.

Isolated subclavian artery dissection is a very rare condition in the absence of trauma or procedures. A 36-year-old woman with a history significant for uncontrolled hypertension presented with a sudden onset of left shoulder and neck pain that woke the patient from sleep. A CT angiogram of the chest revealed a left subclavian artery dissection. The patient was admitted to the hospital for blood pressure control.