A systematic review and meta-analysis of complications associated with crushed cartilage in rhinoplasty.

BACKGROUND: Crushed cartilage grafts improve augmentation and contour irregularities in rhinoplasty; however, they are associated with complications including resorption, asymmetries, palpability, and need for revision surgery. METHODS: A systematic review and meta-analysis following the preferred reporting items for systematic reviews and meta-analyses guidelines was performed on all recorded history up to November 2022 using the search query ("crush" or "crushed") AND cartilage AND rhinoplasty for PubMed, World of Science, Embase, and Cochrane online registries. Data were collected on study information, patient demographics, surgical details, and outcomes. Graft resorption and revision surgery were pooled in a random-effects model, and a subgroup analysis was performed for coverage/non-coverage of the cartilage and degree of crushing. RESULTS: The initial search yielded 163 results, with 11 studies included in the final full-text review. A total of 1132 patients were analyzed, with 456 (40.3%) women, mean age of 48.0 years, and an average follow-up period of 24.9 months. Cartilage resorption rates were statistically higher in graft preparation using severely crushed cartilage (3.4%) compared to non-severely crushed cartilage (0.9%, p = 0.049). There was no significant difference in resorption rate for patients with covered cartilage graft (1.3%) compared to those with non-covered grafts (1.8%, p = 0.7). There were significantly more revision surgeries for severely crushed (17.9%) compared to non-severely crushed (3.5%, p = 0.003) cartilage grafts. CONCLUSIONS: Severely crushed cartilage grafting provides smooth contour and less palpability compared to other degrees of crushing but demonstrates significantly higher rate of resorption.

Novel Drp1 GTPase Inhibitor, Drpitor1a: Efficacy in Pulmonary Hypertension.

BACKGROUND: Drp1 (dynamin-related protein 1), a large GTPase, mediates the increased mitochondrial fission, which contributes to hyperproliferation of pulmonary artery smooth muscle cells in pulmonary arterial hypertension (PAH). We developed a potent Drp1 GTPase inhibitor, Drpitor1a, but its specificity, pharmacokinetics, and efficacy in PAH are unknown. METHODS: Drpitor1a's ability to inhibit recombinant and endogenous Drp1-GTPase was assessed. Drpitor1a's effects on fission were studied in control and PAH human pulmonary artery smooth muscle cells (hPASMC) and blood outgrowth endothelial cells (BOEC). Cell proliferation and apoptosis were studied in hPASMC. Pharmacokinetics and tissue concentrations were measured following intravenous and oral drug administration. Drpitor1a's efficacy in regressing monocrotaline-PAH was assessed in rats. In a pilot study, Drpitor1a reduced PA remodeling only in females. Subsequently, we compared Drpitor1a to vehicles in normal and monocrotaline-PAH females. RESULTS: Drp1 GTPase activity was increased in PAH hPASMC. Drpitor1a inhibited the GTPase activity of recombinant and endogenous Drp1 and reversed the increased fission, seen in PAH hPASMC and PAH BOEC. Drpitor1a inhibited proliferation and induced apoptosis in PAH hPASMC without affecting electron transport chain activity, respiration, fission/fusion mediator expression, or mitochondrial Drp1 translocation. Drpitor1a did not inhibit proliferation or alter mitochondrial dynamics in normal hPASMC. Drpitor1a regressed monocrotaline-PAH without systemic vascular effects or toxicity. CONCLUSIONS: Drpitor1a is a specific Drp1-GTPase inhibitor that reduces mitochondrial fission in PAH hPASMC and PAH BOEC. Drpitor1a reduces proliferation and induces apoptosis in PAH-hPASMC and regresses monocrotaline-PAH. Drp1 is a therapeutic target in PAH, and Drpitor1a is a potential therapy with an interesting therapeutic sexual dimorphism.

Intravenous Acetaminophen Versus Ketorolac for Prehospital Analgesia: A Retrospective Data Review.

BACKGROUND: Parenteral ketorolac and intravenous (IV) acetaminophen have been used for prehospital analgesia, yet limited data exist on their comparative effectiveness. STUDY OBJECTIVES: To evaluate the comparative effectiveness of IV acetaminophen and parenteral ketorolac for analgesia in the prehospital setting. METHODS: We conducted a retrospective cross-sectional evaluation of patients receiving IV acetaminophen or parenteral ketorolac for pain management in a large suburban EMS system between 1/1/2019 and 11/30/2021. The primary outcome was change in first to last pain score. Subgroup analysis was performed on patients with traumatic pain. We used inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) to estimate the treatment effect of acetaminophen versus ketorolac among all patients and the subgroup of those with traumatic pain. RESULTS: Of 2178 patients included, 856 (39.3%) received IV acetaminophen and 1322 (60.7%) received parenteral ketorolac. The unadjusted mean change in pain score was -1.9 (SD 2.4) for acetaminophen group and -2.4 (SD 2.4) for ketorolac. In the propensity score analyses, there was no statistically significant difference in pain score change for the acetaminophen group versus ketorolac among all patients (mean difference, IPTW: 0.11, 95% confidence interval [CI] -0.16, 0.37; PSM: 0.15, 95% CI -0.13, 0.43) and among those with traumatic pain (unadjusted: 0.18, 95% CI -0.35, 0.72; IPTW: 0.23, 95% CI -0.25, 0.71; PSM: -0.03, 95% CI -0.61, 0.54). CONCLUSIONS: We found no statistically significant difference in mean pain reduction of IV acetaminophen and parenteral ketorolac for management of acute pain.

LBTQ parents' needs for support postpartum following a complicated birth: A matter of reproductive justice.

LBTQ people have increased risks of complications during birth, risks potentially driven by minority stress and increased levels of mental illness and fear of childbirth. With the aim of exploring reproductive injustices in postpartum care for LBTQ people, we analyzed qualitative interviews where 22 LBTQ birth and non-birth parents shared their experiences of support needs during the postpartum period after births where complications had arisen. Results point to the importance of providing an LBTQ safe space, which includes the need to feel safe regarding one's gender or sexual identity, by avoiding cisheteronormative assumptions and using inclusive language. In the context of recently experiencing birth complications, parents needed a space where they were able to focus on physical and mental healing. The results further show the need for validation of the non-birth parent and inclusive breast/chest-feeding support. Results emphasize the need for more psychosocial support around the birth experience, including better medical support and information during the whole process of childbirth.

Measurement invariance of the Coparenting Relationship Scale (CRS) across 10 countries.

The purpose of this study was to assess the factor structure and the measurement invariance of the Coparenting Relationship Scale (CRS) across 10 countries based on the seven-factor coparenting model (i.e., Coparenting Agreement, Coparenting Closeness, Exposure to Conflict, Coparenting Support, Endorsement of Partner's Parenting; Division of Labor) proposed by Feinberg (2003). The results of research on coparenting from numerous countries have documented its foundational importance for parent mental health, family relationship quality, child development, and psychopathology. Yet, a cross-country perspective is still lacking. Such a perspective can provide insight into which dimensions of coparenting are universally recognized and which are especially prone to variation. A unique multinational data set, comprised of 15 individual studies collected across 10 countries (Belgium, Brazil, China, Israel, Italy, Japan, Portugal, Switzerland, Turkey, USA) in nine languages was established (N = 9,292; 51.1% mothers). Measurement invariance analyses were conducted. A six-factor structure (original seven factors minus Division of Labor) of the measure was consistent across the different contexts and measurement invariance was achieved at the configural level. There was no support for metric or scalar invariance. These findings provide a basis for the CRS to be used across countries and should inspire future quantitative and qualitative research in cross-country coparenting research to understand what aspects are universal and what aspects of coparenting are linked to specific material, relational, or ideational conditions that underlie high-quality coparenting. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Partner and professional support are associated with father-infant bonding: A cross-sectional analysis of mothers, midwives, and child health nurses' influence on primiparous and multiparous fathers of infants in Sweden.

OBJECTIVE: To assess if received professional and social support are associated with father-infant bonding among primiparous (first-time) and multiparous (multi-time) fathers. BACKGROUND: Early father-infant bonding predicts several positive child outcomes. However, while received professional and social support positively impacts fathers' transition into parenthood, little research has tested if these factors are associated with a stronger father-infant bond. METHODS: In total, 499 fathers (296 primiparous and 203 multiparous) of infants (aged 0-12 months) completed a cross-sectional online survey between November 2018 and March 2020. The survey included items related to socio-demographics, having a planned pregnancy, postnatal midwifery support, child health nurse support, child health center attendance, and social support. The parent-infant bonding questionnaire (PBQ) was used to assess the father-infant bond. Multiple linear regression models were estimated for the total sample and based on paternal parity. Missing data were managed through multiple imputation procedures. FINDINGS: Fathers reported fewer bonding disturbances if they received support from their partners, postnatal midwives, child health nurses, and attended more child health visits. Primiparous fathers reported fewer bonding disturbances when receiving support from their partners, postnatal midwives, and the child health nurse. However, multiparous fathers had more bonding disturbances than primiparous fathers and received less professional and partner support. CONCLUSIONS: Receiving more partner and professional support is associated with less father-infant bonding disturbances. To encourage a better father-infant bond, clinicians should invite and support all fathers, regardless of parity, as they transition to parenthood.

The Role of Imaging for Gastrointestinal Bleeding: Consensus Recommendations From the American College of Gastroenterology and Society of Abdominal Radiology.

Gastrointestinal (GI) bleeding is the most common GI diagnosis leading to hospitalization within the United States. Prompt diagnosis and treatment of GI bleeding is critical to improving patient outcomes and reducing high healthcare utilization and costs. Radiologic techniques including computed tomography angiography, catheter angiography, computed tomography enterography, magnetic resonance enterography, nuclear medicine red blood cell scan, and technetium-99m pertechnetate scintigraphy (Meckel scan) are frequently used to evaluate patients with GI bleeding and are complementary to GI endoscopy. However, multiple management guidelines exist which differ in the recommended utilization of these radiologic examinations. This variability can lead to confusion as to how these tests should be used in the evaluation of GI bleeding. In this document, a panel of experts from the American College of Gastroenterology and Society of Abdominal Radiology provide a review of the radiologic examinations used to evaluate for GI bleeding including nomenclature, technique, performance, advantages, and limitations. A comparison of advantages and limitations relative to endoscopic examinations is also included. Finally, consensus statements and recommendations on technical parameters and utilization of radiologic techniques for GI bleeding are provided.

Rapid Creation of Knowledge-Balanced Student Groups Using ChatGPT4.

We demonstrated use of ChatGPT4 for efficient group formation in undergraduate medical education. ChatGPT4 created balanced groups considering students' backgrounds in microbiology, physiology, genetics, and immunology considerably faster than manual efforts. Manual refinements included gender balance and discipline distribution. Improvements included ChatGTP's ability to further incorporate GPA and MCAT scores.

Cluster Analysis of Fear of Childbirth, Anxiety, Depression, and Childbirth Self-Efficacy.

OBJECTIVE: To identify clusters of women based on anxiety, depression, fear of birth, and childbirth self-efficacy and factors associated with the clusters. DESIGN: Cross-sectional survey. SETTING: Online in Sweden. PARTICIPANTS: Pregnant women (N = 1,419). METHODS: We collected data through online questionnaires. We included scales to measure anxiety, depression, worries about and fear of birth, and self-efficacy in a kappa-means cluster analysis. We calculated odds ratios with 95% confidence intervals between clusters and background variables. RESULTS: We identified 4 clusters based on severity: Resourceful-Robust, Resourceful-Fearful, Vulnerable-Fearful, and Fragile-Fearful. Participants in the Resourceful-Fearful and Vulnerable-Fearful clusters were more likely to report mental health problems than those in the Resourceful-Robust cluster. Participants in the Vulnerable-Fearful and Fragile-Fearful clusters were more likely to report mental health problems than those in the Resourceful-Robust cluster. Participants in the Fragile-Fearful cluster were more likely to be multiparous, report that their pregnancy was not normal, and prefer cesarean birth than those in the Resourceful-Robust cluster. CONCLUSIONS: Women with childbirth fear may be vulnerable to anxiety and depression during the perinatal period, although the severity might vary. Self-efficacy might be a mediator against mental health problems. Findings demonstrated levels of severity, and the one-size-fits-all approach in Swedish health care may benefit from a more targeted approach for women with fear of childbirth.

Preferences of support and barriers and facilitators to help-seeking in pregnant women with severe fear of childbirth in Sweden: a mixed-method study.

BACKGROUND: There are few support interventions for women with fear of childbirth tailored towards type of fears and parity. To inform the future development of an acceptable and relevant intervention for women with severe fear of childbirth, primary objectives were to examine: (1) pregnant women's experiences of and preferences for support and (2) barriers and facilitators to help-seeking. Secondary objectives were to examine if there are any differences based on pregnant women's parity. METHODS: Pregnant women with a severe fear of childbirth in Sweden completed an online cross-sectional survey between February and September 2022. Severe fear of childbirth was measured using the fear of childbirth scale. Quantitative data were analysed using descriptive and inferential statistics and free answers were analysed using manifest content analysis. A contiguous approach to integration was adopted with qualitative and quantitative findings reported separately. RESULTS: In total, 609 participants, 364 nulliparous and 245 parous women, had severe fear of childbirth. The main category "A twisting road to walk towards receiving support for fear of childbirth" was explored and described by the generic categories: Longing for support, Struggling to ask for support, and Facilitating aspects of seeking support. Over half (63.5%), of pregnant women without planned or ongoing treatment, wanted support for fear of childbirth. Most (60.2%) pregnant women with ongoing or completed fear of childbirth treatment regarded the treatment as less helpful or not at all helpful. If fear of childbirth treatment was not planned, 35.8% of women would have liked to have received treatment. Barriers to help seeking included stigma surrounding fear of childbirth, previous negative experiences with healthcare contacts, fear of not being believed, fear of not being listened to, and discomfort of having to face their fears. Facilitators to help seeking included receiving respectful professional support that was easily available, flexible, and close to home. CONCLUSIONS: Most pregnant women with severe fear of childbirth felt unsupported during pregnancy. Findings emphasise the need to develop individual and easily accessible psychological support for women with severe fear of childbirth, delivered by trained professionals with an empathetic and respectful attitude.

Learning nonparametric ordinary differential equations from noisy data.

Learning nonparametric systems of Ordinary Differential Equations (ODEs) x˙=f(t,x) from noisy data is an emerging machine learning topic. We use the well-developed theory of Reproducing Kernel Hilbert Spaces (RKHS) to define candidates for f for which the solution of the ODE exists and is unique. Learning f consists of solving a constrained optimization problem in an RKHS. We propose a penalty method that iteratively uses the Representer theorem and Euler approximations to provide a numerical solution. We prove a generalization bound for the L2 distance between x and its estimator. Experiments are provided for the FitzHugh-Nagumo oscillator, the Lorenz system, and for predicting the Amyloid level in the cortex of aging subjects. In all cases, we show competitive results compared with the state-of-the-art.

Prehospital Surgical Cricothyrotomy in a Ground-Based 9-1-1 EMS System: A Retrospective Review.

BACKGROUND: Airway management is a cornerstone in the prehospital care of critically ill or injured patients. Surgical cricothyrotomy offers a rapid and effective solution when oxygenation and ventilation fail using less-invasive techniques. However, the exact indications, incidence, and success of prehospital surgical cricothyrotomy are unknown, with variable rates reported in the literature. This study aimed to examine prehospital indications and success rates for surgical cricothyrotomy within a large, suburban, ground-based Emergency Medical Services (EMS) system. METHODS: This is a retrospective analysis of 31 patients who underwent paramedic performed surgical cricothyrotomy from 2012 through 2022. Key demographic parameters were analyzed, including the incidence of cardiac arrest, call type (trauma versus medical), initial airway management attempts, number of endotracheal intubation (ETI) attempts before surgical airway, and average time to the establishment of a surgical airway in relation to the number of ETI attempts. Surgical cricothyrotomy success was defined as the acquisition of four-phase end-tidal capnography reading. The primary data sources were the EMS electronic medical records, and descriptive statistics were calculated. RESULTS: A total of 31 patients were included in the final analysis. Of those who received a surgical cricothyrotomy, 42% (13/31) occurred in the trauma setting, while 58% (18/31) were medical calls. In all patients who underwent surgical cricothyrotomy, the median (IQR) time to the procedure was 17 minutes (IQR = 11-24). In trauma patients, the median time to surgical cricothyrotomy was 12 minutes (IQR = 9-19) versus 19 minutes (IQR = 14-33) in medical patients. End-tidal carbon dioxide (ETCO2) detection and placement success was confirmed in 94% (29/31) of patients. Endotracheal intubation was attempted in 55% (17/31) before subsequent surgical cricothyrotomy, with 29% (9/31) receiving more than one ETI attempt. The median time to surgical cricothyrotomy when multiple prior intubation attempts occurred was 33 minutes (IQR = 23-36) compared to 14.5 minutes (IQR = 6-19) in patients without a preceding intubation attempt. CONCLUSION: Prehospital surgical airway can be performed by paramedics with a high degree of success. Identification of the need for surgical cricothyrotomy should be determined as soon as possible to allow for rapid securement of the airway and to ensure adequate oxygenation and ventilation.

The Role of Imaging for GI Bleeding: ACG and SAR Consensus Recommendations.

Gastrointestinal (GI) bleeding is the most common GI diagnosis leading to hospitalization within the United States. Prompt diagnosis and treatment of GI bleeding is critical to improving patient outcomes and reducing high health care utilization and costs. Radiologic techniques including CT angiography, catheter angiography, CT enterography, MR enterography, nuclear medicine red blood cell scan, and technetium-99m pertechnetate scintigraphy (Meckel scan) are frequently used to evaluate patients with GI bleeding and are complementary to GI endoscopy. However, multiple management guidelines exist, which differ in the recommended utilization of these radiologic examinations. This variability can lead to confusion as to how these tests should be used in the evaluation of GI bleeding. In this document, a panel of experts from the American College of Gastroenterology and Society of Abdominal Radiology provide a review of the radiologic examinations used to evaluate for GI bleeding including nomenclature, technique, performance, advantages, and limitations. A comparison of advantages and limitations relative to endoscopic examinations is also included. Finally, consensus statements and recommendations on technical parameters and utilization of radiologic techniques for GI bleeding are provided. © Radiological Society of North America and the American College of Gastroenterology, 2024. Supplemental material is available for this article. This article is being published concurrently in American Journal of Gastroenterology and Radiology. The articles are identical except for minor stylistic and spelling differences in keeping with each journal's style. Citations from either journal can be used when citing this article. See also the editorial by Lockhart in this issue.

Protocol for neurogenin-2-mediated induction of human stem cell-derived neural progenitor cells.

Human pluripotent stem cell-derived neural progenitor cells (NPCs) are an essential tool for the study of brain development and developmental disorders such as autism. Here, we present a protocol to generate NPCs rapidly and reproducibly from human stem cells using dual-SMAD inhibition coupled with a brief pulse of mouse neurogenin-2 (Ngn2) overexpression. We detail the 48-h induction scheme deployed to produce these cells-termed stem cell-derived Ngn2-accelerated progenitor cells-followed by steps for expansion, purification, banking, and quality assessment. For complete details on the use and execution of this protocol, please refer to Wells et al.1.

Ammonia-oxidizing bacteria and archaea exhibit differential nitrogen source preferences.

Ammonia-oxidizing microorganisms (AOM) contribute to one of the largest nitrogen fluxes in the global nitrogen budget. Four distinct lineages of AOM: ammonia-oxidizing archaea (AOA), beta- and gamma-proteobacterial ammonia-oxidizing bacteria (ß-AOB and γ-AOB) and complete ammonia oxidizers (comammox), are thought to compete for ammonia as their primary nitrogen substrate. In addition, many AOM species can utilize urea as an alternative energy and nitrogen source through hydrolysis to ammonia. How the coordination of ammonia and urea metabolism in AOM influences their ecology remains poorly understood. Here we use stable isotope tracing, kinetics and transcriptomics experiments to show that representatives of the AOM lineages employ distinct regulatory strategies for ammonia or urea utilization, thereby minimizing direct substrate competition. The tested AOA and comammox species preferentially used ammonia over urea, while ß-AOB favoured urea utilization, repressed ammonia transport in the presence of urea and showed higher affinity for urea than for ammonia. Characterized γ-AOB co-utilized both substrates. These results reveal contrasting niche adaptation and coexistence patterns among the major AOM lineages.

Data Requirement for Animal-Derived Wound Care Devices: Limitations of the 510(k) Regulatory Pathway.

BACKGROUND: Device classification and preclinical data requirements for animal-derived wound care products were recently reviewed by the FDA. Given the possible performance differences for these products, we evaluated the FDA data requirements as well as the published literature for all animal-derived wound care products ever cleared through the FDA. STUDY DESIGN: The publicly available online database was queried for all animal-derived wound products; premarket data requirements for each product were recorded. A PubMed search was conducted to determine the number of published clinical studies for each product, and manufacturer websites were accessed to obtain the price for each product. RESULTS: A total of 132 animal-derived wound products have been cleared by the FDA since the Center for Devices and Radiological Health was established in 1976. Of these, 114 had a publicly available clearance statement online. Preclinical biocompatibility testing was performed in 85 products (74.6%) and referenced in 10 (8.8%). Preclinical animal wound healing testing took place in 17 (14.9%). Only 9 products (7.9%) had clinical safety testing, and no products had clinical effectiveness data. We found no published peer-reviewed clinical data for 97 products (73%). Cost was infrequently available but ranged from $4.79 to $2,178 per unit. CONCLUSIONS: Although the current pathway is appropriate for efficiently clearing new wound care products, clinical effectiveness is not included in the regulatory review process. Wound care products are primarily evaluated by the FDA for safety and biocompatibility. Thus, any claims of clinical effectiveness require independent validation, which is often lacking.

Imaging of Fontan-Associated Liver Disease.

ABSTRACT: The Fontan procedure is the definitive treatment for patients with single-ventricle physiology. Surgical advances have led to a growing number of patients surviving into adulthood. Fontan-associated liver disease (FALD) encompasses a spectrum of pathologic liver changes that occur secondary to altered physiology including congestion, fibrosis, and the development of liver masses. Assessment of FALD is difficult and relies on using imaging alongside of clinical, laboratory, and pathology information. Ultrasound, computed tomography, and magnetic resonance imaging are capable of demonstrating physiologic and hepatic parenchymal abnormalities commonly seen in FALD. Several novel imaging techniques including magnetic resonance elastography are under study for use as biomarkers for FALD progression. Imaging has a central role in detection and characterization of liver masses as benign or malignant. Benign FNH-like masses are commonly encountered; however, these can display atypical features and be mistaken for hepatocellular carcinoma (HCC). Fontan patients are at elevated risk for HCC, which is a feared complication and has a poor prognosis in this population. While imaging screening for HCC is widely advocated, no consensus has been reached regarding an optimal surveillance regimen.

Same-Day Discharge for Immediate Breast Reconstruction: A National Surgical Quality Improvement Program Study.

BACKGROUND: Patients undergoing immediate breast reconstruction with tissue expanders are frequently admitted after surgery for monitoring and pain control, which introduces additional costs and risks of nosocomial infection. Same-day discharge could conserve resources, mitigate risk, and return patients home for faster recovery. The authors used large data sets to investigate the safety of same-day discharge after mastectomy with immediate postoperative expander placement. METHODS: A retrospective review was performed of patients in the National Surgical Quality Improvement Program database who underwent breast reconstruction using tissue expanders between 2005 and 2019. Patients were grouped based on date of discharge. Demographic information, medical comorbidities, and outcomes were recorded. Statistical analysis was performed to determine efficacy of same-day discharge and identify factors that predict safety. RESULTS: Of the 14,387 included patients, 10% were discharged the same day, 70% on postoperative day 1, and 20% later than postoperative day 1. The most common complications were infection, reoperation, and readmission, which trended upward with length of stay (6.4% versus 9.3% versus 16.8%), but were statistically equivalent between same-day and next-day discharge. The complication rate for later-day discharge was statistically higher. Patients discharged later had significantly more comorbidities than same or next-day discharge counterparts. Predictors of complications included hypertension, smoking, diabetes, and obesity. CONCLUSIONS: Patients undergoing mastectomy with immediate tissue expander reconstruction are usually admitted overnight. However, same-day discharge was demonstrated to have an equivalent risk of perioperative complications as next-day discharge. For the otherwise healthy patient, going home the day of surgery is a safe and cost-effective option, although the decision should be made based on the individual patient. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Lack of patient and primary care physician follow-up in geriatric emergency department patients with head trauma from a fall.

STUDY OBJECTIVE: Falls are the leading cause of injuries in the US for older adults. Follow-up after an ED-related fall visit is essential to initiate preventive strategies in these patients who are at very high risk for recurrent falls. It is currently unclear how frequently follow-up occurs and whether preventive strategies are implemented. Our objective is to determine the rate of follow-up by older adults who sustain a fall related head injury resulting in an ED visit, the rate and type of risk assessment and adoption of preventive strategies. METHODS: This 1-year prospective observational study was conducted at two South Florida hospitals. All older ED patients with an acute head injury due to a fall were identified. Telephone surveys were conducted 14 days after ED presentation asking about PCP follow-up and adoption of fall prevention strategies. Clinical and demographic characteristics were compared between patients with and without follow up. RESULTS: Of 4951 patients with a head injury from a fall, 1527 met inclusion criteria. 905 reported follow-up with their PCP. Of these, 72% reported receiving a fall assessment and 56% adopted a fall prevention strategy. Participants with PCP follow-up were significantly more likely to have a history of cancer or hypertension. CONCLUSION: Only 60% of ED patients with fall-related head injury follow-up with their PCP. Further, 72% received a fall assessment and only 56% adopted a fall prevention strategy. These data indicate an urgent need to promote PCP fall assessment and adoption of prevention strategies in these patients.

Biallelic loss-of-function variants in CACHD1 cause a novel neurodevelopmental syndrome with facial dysmorphism and multisystem congenital abnormalities.

PURPOSE: We established the genetic etiology of a syndromic neurodevelopmental condition characterized by variable cognitive impairment, recognizable facial dysmorphism, and a constellation of extra-neurological manifestations. METHODS: We performed phenotypic characterization of 6 participants from 4 unrelated families presenting with a neurodevelopmental syndrome and used exome sequencing to investigate the underlying genetic cause. To probe relevance to the neurodevelopmental phenotype and craniofacial dysmorphism, we established two- and three-dimensional human stem cell-derived neural models and generated a stable cachd1 zebrafish mutant on a transgenic cartilage reporter line. RESULTS: Affected individuals showed mild cognitive impairment, dysmorphism featuring oculo-auriculo abnormalities, and developmental defects involving genitourinary and digestive tracts. Exome sequencing revealed biallelic putative loss-of-function variants in CACHD1 segregating with disease in all pedigrees. RNA sequencing in CACHD1-depleted neural progenitors revealed abnormal expression of genes with key roles in Wnt signaling, neurodevelopment, and organ morphogenesis. CACHD1 depletion in neural progenitors resulted in reduced percentages of post-mitotic neurons and enlargement of 3D neurospheres. Homozygous cachd1 mutant larvae showed mandibular patterning defects mimicking human facial dysmorphism. CONCLUSION: Our findings support the role of loss-of-function variants in CACHD1 as the cause of a rare neurodevelopmental syndrome with facial dysmorphism and multisystem abnormalities.