Does a delay to surgery for preoperative echocardiogram affect outcomes in patients with hip fracture?

Introduction: Delay to surgery >24 hours has been shown to correlate with mortality rates in patients with hip fracture when left untreated. Many of these patients have multiple comorbidities, including aortic stenosis (AS), and undergo workup for operative clearance, which may delay time to surgery. The purpose of this study was to examine whether preoperative echocardiogram workup affects time to surgery, complications, and mortality after operative fixation for hip fracture. Methods: Our institutional hip fracture registry was retrospectively reviewed for inclusion over a 3-year period. Patients who had a preoperative echocardiogram (yECHO) for operative clearance were compared with those who did not (nECHO). Demographic data, time to surgery, overall complication rate, and mortality at 30 days, 90 days, and 1 year were collected. Results: Two cohorts consisted of 136 yECHO patients (45.8%) and 161 nECHO patients (54.2%). Thirty-two yECHO patients (23.5%) had AS. Patients in the yECHO cohort were more likely to have a complication for any cause compared with nECHO patients (25.7% vs. 10.6%, P = 0.01) and have a higher mortality rate at 1 year (38.9% vs. 17.4%, P = 0.001). There was no association found between AS and all-cause complication (P = 0.54) or 30-day (P = 0.13) or 90-day mortality rates (P = 0.79). However, patients with AS had a significantly higher mortality rate at 1 year (45.8% vs. 25.1%, P = 0.03). Conclusion: This study reinforces the benefits of ensuring less than a 24-hour time to surgery in the setting of a hip fracture and identifies an area of preoperative management that can be further optimized to prevent unnecessary prolongation in time to surgery. Patients with known aortic stenosis are not associated with increased 30-day or 90-day mortality or all-cause complications. Surgical delays in the yECHO cohort were attributed to preoperative medical assessments, including echocardiograms and the management of comorbidities. Therefore, the selective utilization of preoperative echocardiograms is needed and should be reserved to ensure they have a definitive role in guiding the perioperative care of patients with hip fracture. Level of Evidence: III.

Comparative outcomes after treatment of peri-implant, periprosthetic, and interprosthetic femur fractures: which factors increase mortality risk?

Objectives: To compare mortality rates between patients treated surgically for periprosthetic fractures (PPF) after total hip arthroplasty (THA), total knee arthroplasty (TKA), peri-implant (PI), and interprosthetic (IP) fractures while identifying risk factors associated with mortality following PPF. Design: Retrospective. Setting: Single, Level II Trauma Center. Patients/Participants: A retrospective review was conducted of 129 consecutive patients treated surgically for fractures around a pre-existing prosthesis or implant from 2013 to 2020. Patients were separated into 4 comparison groups: THA, TKA, PI, and IP fractures. Intervention: Revision implant or arthroplasty, open reduction and internal fixation (ORIF), intramedullary nailing (IMN), percutaneous screws, or a combination of techniques. Main Outcome Measurements: Primary outcome measures include mortality rates of different types of PPF, PI, and IP fractures at 1-month, 3-month, 6-month, 1-year, and 2-year postoperative. We analyzed risk factors associated with mortality aimed to determine whether treatment type affects mortality. Results: One hundred twenty-nine patients were included for final analysis. Average follow-up was similar between all groups. The overall 1-year mortality rate was 1 month (5%), 3 months (12%), 6 months (13%), 1 year (15%), and 2 years (22%). There were no differences in mortality rates between each group at 30 days, 90 days, 6 months, 1 year, and 2 years (P-value = 0.86). A Kaplan-Meier survival curve demonstrated no difference in survivorship up to 2 years. Older than 65 years, history of hypothyroidism and dementia, and discharge to a skilled nursing facility (SNF) led to increased mortality. There was no survival benefit in treating patients with PPFs with either revision, ORIF, IMN, or a combination of techniques. Conclusion: The overall mortality rates observed were 1 month (5%), 3 months (12%), 6 months (13%), 1 year (15%), and 2 years (22%), and no differences were found between each group at all follow-up time points. Patients aged 65 and older with a history of hypothyroidism and/or dementia discharged to an SNF are at increased risk for mortality. From a mortality perspective, surgeons should not hesitate to choose the surgical treatment they feel most comfortable performing. Level of Evidence: Level III.

Enhancing Physician Advocacy Through Collaboration With Government Relations: Report From the Health Policy Scholars Program.

OBJECTIVE: To explore barriers, facilitators, and benefits of collaboration between academic pediatricians and institutional offices of government relations (OGR) to enhance policy advocacy efforts. METHODS: The Academic Pediatric Associations' Health Policy Scholars met with the government relations team in their affiliated institutions as part of their experiential learning curriculum. Afterward, they submitted written reflections, which were coded and analyzed using inductive qualitative content analysis to identify key themes. RESULTS: Reflections were completed by 21 of 23 (91.3%) participants. Most participants (76.2%) were faculty at free-standing children's hospitals and had been at their institutions <5 years (52.3%) or 5 to 10 years (33.3%). Institutional OGR structure varied widely and not all institutions had well-defined priorities. Key themes of the reflections included that OGRs often had dynamic priorities and fiscal considerations frequently took precedence. Barriers to physician involvement with OGR are often related to difficulty identifying the correct staff contact and not having the time and support for advocacy work. Facilitators included leveraging existing relationships and collaborations, including those of peer or mentor connections to the OGR staff. Anticipated benefits to both OGR and physicians included improved knowledge of advocacy opportunities, enhanced advocacy efforts leveraging physicians' expertise and patient stories, and message alignment and amplification of physician and institutional advocacy work. CONCLUSIONS: Collaboration between physician-advocates and institutional OGR is feasible and, with orientation and mentorship, may facilitate improved physician and institutional policy advocacy efforts. Supporting this type of collaboration may enhance physician and institutional advocacy on behalf of their shared patients and communities.

Comparison of Outcomes After Reverse Total Shoulder Arthroplasty in Patients With Proximal Humerus Fractures Versus Rotator Cuff Arthropathy.

INTRODUCTION: Indications for reverse total shoulder arthroplasty (rTSA) has expanded to encompass complex proximal humerus fractures (PHFs) in recent years. The purpose of this study was to report and assess whether PHF patients treated with rTSA could achieve similar functional outcomes and short-term survivorship to patients who underwent rTSA for rotator cuff arthropathy (RTCA). METHODS: All consecutive patients with a preoperative diagnosis of PHF or RTCA, 18 years or older, treated with rTSA at a single academic institution between 2018 and 2020 with a minimum 2-year follow-up were retrospectively reviewed. Primary outcomes were survivorship defined as revision surgery or implant failure analyzed using the Kaplan-Meier survival curve, and functional outcomes, which included Quick Disabilities of the Arm, Shoulder, and Hand, and range of motion (ROM) were compared at multiple follow-up time points up to 2 years. Secondary outcomes were patient demographics, comorbidities, surgical data, length of hospital stay, and discharge disposition. RESULTS: A total of 48 patients were included: 21 patients (44%) were diagnosed with PHF and 27 patients (56%) had RTCA. The Kaplan-Meier survival rate estimates at 3 years were 90.5% in the PHF group and 85.2% in the RTCA group. No differences in revision surgery rates between the two groups (P = 0.68) or survivorship (P = 0.63) were found. ROM was significantly lower at subsequent follow-up time points in multiple planes (P < 0.05). A greater proportion of patients in the PHF group received cement for humeral implant fixation compared with the RTCA group (48% versus 7%, P = 0.002). The mean length of hospital stay was longer in PHF patients compared with RTCA patients (2.9 ± 3.8 days versus 1.6 ± 1.8 days, P = 0.13), and a significantly lower proportion of PHF patients were discharged home (67% versus 96%, P = 0.015). CONCLUSION: The rTSA implant survivorship at 3 years for both PHF and RTCA patients show comparable results. At the 2-year follow-up, RTCA patients treated with rTSA were found to have better ROM compared with PHF patients.

Five-year Results from the Prospective, Multicenter, Observational SOUNDS Study of Patients with Overactive Bladder Treated with the InterStim System for Sacral Neuromodulation.

BACKGROUND: Although sacral neuromodulation (SNM) for overactive bladder (OAB) is an established therapy, there is a lack of high-quality, long-term data on real-life practice. OBJECTIVE: To report on real-life therapeutic effectiveness, quality of life (QoL), disease severity, and safety as well as patient-reported symptom bother after approximately 5 yr of follow-up. DESIGN, SETTING, AND PARTICIPANTS: A total of 291 OAB patients were enrolled at 25 French sites according to local standard of care. Sacral neuromOdUlation with InterStim therapy for intractable lower uriNary tract DySfunctions (SOUNDS) enrolled both de novo and replacement patients, and a total of 229 patients were permanently implanted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Over the course of the study, patients were followed up six times with two follow-ups in the year after implantation and annually thereafter. Of the patients, 154 completed the final follow-up after a mean of 57.7 ± 3.9 mo. RESULTS AND LIMITATIONS: The mean number of daily leaks in urinary urge incontinence (UI) patients was reduced from 4.4 ± 3.3 at baseline to 1.8 ± 2.6 after 5 yr in de novo and from 5.4 ± 4.9 to 2.2 ± 3.0 in replacement patients (both p < 0.001). Likewise, the number of voids in urinary frequency patients was reduced compared with baseline (de novo: reduced from 12.6 ± 4.0 [baseline] to 9.6 ± 4.3 [5 yr]; replacements: reduced from 11.5 ± 4.3 [baseline] to 9.2 ± 3.1 [5 yr]; both p < 0.05). Complete continence rates after 5 yr were 44% (25/57) in de novo and 33% (5/15) in replacement UI patients, and 68% (39/57) and 67% (10/15) of UI patients were categorized as therapy responders by showing a >50% improvement in leaks. Disease severity (Urinary Symptom Profile domain 2), Numeric Rating Scale-based symptom bother, and disease-specific QoL (Ditrovie) improved significantly in both groups at all visits (p < 0.001). Adverse events related to device or procedure occurred in 51% (140/274) of patients, with 66% (152/229) of the events being classified as minor (Clavien-Dindo grade I and II). Surgical revisions were reported in 39% (89/229), which include permanent explants in 15% (34/229) of patients. CONCLUSIONS: SOUNDS demonstrates the sustained effectiveness and QoL improvements of SNM in OAB patients after 5 yr in real-world conditions while maintaining an acceptable safety profile consistent with literature. PATIENT SUMMARY: This study confirmed that French overactive bladder patients had a sustained symptom and bother reduction, and improvements in quality of life up to 5 yr after sacral neuromodulation device implantation.

Child Advocacy in Action: If Not You, Who? If Not now, When?

The notion that the physician has a responsibility to both the patient in their care and the community in which they reside has been a source of inspiration and tension within the profession for centuries. The profession of Pediatrics has uniquely incorporated advocacy into its training programs and will likely continue to incorporate advocacy into its professional standards for the foreseeable future. In this article, we review the history of advocacy within the profession, outline the skills needs for successful child health advocacy and offer examples of how advocacy combined with pediatric practice has improved the lives of children.

Direct versus indirect posterior malleolar fixation in the treatment of trimalleolar ankle fractures: Is there a difference in outcomes?

Purpose: The purpose of this study was to examine the differences in functional outcomes between direct and indirect surgical fixation methods of the posterior malleolus in the setting of trimalleolar fractures and identify any variables affecting patient outcomes. Methods: Primary outcomes were evaluated by PROMIS scores for short-term outcomes regarding total pain (TP) and total function (TF) comparing 40 patients with direct fixation with 77 with indirect fixation. Continuous variables were analyzed using t tests for parametric variables and the Mann-Whitney U test for nonparametric variables. Categorical variables were analyzed using a χ2 test. Univariate and multivariate linear regression models were performed to analyze factors that affect outcomes of TP and TF. Results: There was no difference in TP or TF between groups (P = 0.65 vs. P = 0.19). On univariate linear regression for TP, BMI, incidence of complication, tobacco use, and open injury showed significance in increasing pain levels with open injuries providing the greatest effect (coef = 11.8). On multivariate analysis, BMI, incidence of complication, open injury, and tourniquet time all significantly increased pain. For TF, univariate analysis showed age, BMI, incidence of complication, and diabetes to decrease function, and use of external fixator and tourniquet time increased function. In the multivariate model, increased BMI, open injuries, and increasing tourniquet time all decreased TF while use of an external fixator increased TF. Conclusion: This study showed no difference in TP and TF using the PROMIS outcome scores when comparing direct fixation versus indirect fixation under univariate and multivariate models. Level of Evidence: Therapeutic III.

A thalamo-preoptic pathway promotes social grooming in rodents.

Social touch is an essential component of communication. Little is known about the underlying pathways and mechanisms. Here, we discovered a novel neuronal pathway from the posterior intralaminar thalamic nucleus (PIL) to the medial preoptic area (MPOA) involved in the control of social grooming. We found that the neurons in the PIL and MPOA were naturally activated by physical contact between female rats and also by the chemogenetic stimulation of PIL neurons. The activity-dependent tagging of PIL neurons was performed in rats experiencing physical social contact. The chemogenetic activation of these neurons increased social grooming between familiar rats, as did the selective activation of the PIL-MPOA pathway. Neurons projecting from the PIL to the MPOA express the neuropeptide parathyroid hormone 2 (PTH2), and the central infusion of its receptor antagonist diminished social grooming. Finally, we showed a similarity in the anatomical organization of the PIL and the distribution of the PTH2 receptor in the MPOA between the rat and human brain. We propose that the discovered neuronal pathway facilitates physical contact with conspecifics.

Transcriptome Profiling of the Dorsomedial Prefrontal Cortex in Suicide Victims.

The default mode network (DMN) plays an outstanding role in psychiatric disorders. Still, gene expressional changes in its major component, the dorsomedial prefrontal cortex (DMPFC), have not been characterized. We used RNA sequencing in postmortem DMPFC samples to investigate suicide victims compared to control subjects. 1400 genes differed using log2FC > ±1 and adjusted p-value < 0.05 criteria between groups. Genes associated with depressive disorder, schizophrenia and impaired cognition were strongly overexpressed in top differentially expressed genes. Protein−protein interaction and co-expressional networks coupled with gene set enrichment analysis revealed that pathways related to cytokine receptor signaling were enriched in downregulated, while glutamatergic synaptic signaling upregulated genes in suicidal individuals. A validated differentially expressed gene, which is known to be associated with mGluR5, was the N-terminal EF-hand calcium-binding protein 2 (NECAB2). In situ hybridization histochemistry and immunohistochemistry proved that NECAB2 is expressed in two different types of inhibitory neurons located in layers II-IV and VI, respectively. Our results imply extensive gene expressional alterations in the DMPFC related to suicidal behavior. Some of these genes may contribute to the altered mental state and behavior of suicide victims.

Behavioural actions of tuberoinfundibular peptide 39 (parathyroid hormone 2).

Tuberoinfundibular peptide of 39 residues (TIP39) acts via its endogenous class B G-protein coupled receptorthe parathyroid hormone 2 receptor (PTH2R). Hence, it is also known as parathyroid hormone 2. The peptide is expressed in the brain by a small number of neurons with a highly restricted distribution, which in turn project to a large number of brain regions that contain PTH2R. This peptide neuromodulator system has been extensively investigated over the past 20 years including its behavioural actions, such as its role in the control of nociception, fear and fear incubation, anxiety and depression-like behaviours, and maternal and social behaviours. It also influences thermoregulation and potentially auditory responses. TIP39 probably exerts direct effect on the neuronal networks controlling these behaviours based on the localization of PTH2R and local TIP39 actions. In addition, TIP39 also affects the secretion of several hypothalamic hormones providing the basis for indirect behavioural actions. Recently developed experimental tools have stimulated further behavioural investigations, and novel results obtained are discussed in this review.

Tracking Highly Similar Rat Instances under Heavy Occlusions: An Unsupervised Deep Generative Pipeline.

Identity tracking and instance segmentation are crucial in several areas of biological research. Behavior analysis of individuals in groups of similar animals is a task that emerges frequently in agriculture or pharmaceutical studies, among others. Automated annotation of many hours of surveillance videos can facilitate a large number of biological studies/experiments, which otherwise would not be feasible. Solutions based on machine learning generally perform well in tracking and instance segmentation; however, in the case of identical, unmarked instances (e.g., white rats or mice), even state-of-the-art approaches can frequently fail. We propose a pipeline of deep generative models for identity tracking and instance segmentation of highly similar instances, which, in contrast to most region-based approaches, exploits edge information and consequently helps to resolve ambiguity in heavily occluded cases. Our method is trained by synthetic data generation techniques, not requiring prior human annotation. We show that our approach greatly outperforms other state-of-the-art unsupervised methods in identity tracking and instance segmentation of unmarked rats in real-world laboratory video recordings.

Use of antibiotic-cement coated locking plates in the setting of periprosthetic infection and infected nonunion.

INTRODUCTION: In the setting of periprosthetic total hip and knee arthroplasty (THA/TKA) infection, plating of the femur may be necessary for fracture fixation, prophylactic fixation of the femur, poor bone quality, or infected femoral shaft nonunion. The purpose of this study was to investigate infection control rates and fracture healing in patients receiving antibiotic cement coated plates in the setting of infected nonunion and periprosthetic infections. METHODS: We retrospectively reviewed a series of ten patients who had an antibiotic coated plate placed in the setting of periprosthetic infection or infected nonunion with a minimum follow-up of six months. 80 g of Simplex bone cement (Stryker, Mahwah, NJ) were mixed with 4 g of powdered vancomycin and 4.8 g of powdered tobramycin and applied to a dynamic compression plate with locking screw guides in every hole. The antibiotic loaded cement was allowed to harden before implantation. Outcome measures were designed to assess for fracture healing defined as three out of four cortices united on radiographs along with bearing full weight without pain and evidence of infection control defined as normalized erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in the absence of antibiotic treatment with no clinical signs of infection. RESULTS: Ten patients were treated with an antibiotic cement coated plate in the settings of infectious nonunion and periprosthetic infection and followed for an average of three years (mean 21.4 months, seven months to 61 months). Eight patients (80%) went on to successful control of infection after initial procedure. Two patients developed chronic drainage and had a second antibiotic spacer with antibiotic cement coated plate placed before the infection was controlled. All patients obtained successful control of infection at latest follow-up showing no clinical signs of infection, normalized laboratory markers, and negative culture results. There were no reported mechanical failures of the implant, fractures of the femur, or soft tissue complications. CONCLUSION: An antibiotic cement coated plating technique is a viable option for periprosthetic THA and TKA infections requiring plating of the femur or in patients with an infected nonunion.

Dual regulation of miR-375 and CREM genes in pancreatic beta cells.

MicroRNA-375 (miR-375) is upregulated in the islets of some diabetics and is correlated with poor outcome. Previous work in our laboratory showed that cyclic adenosine monophosphate (cAMP) reduces miR-375 expression and could provide a way to restore normal miR-375 levels, however the transcription repression mechanism is unknown. Using a chromatin immunoprecipitation assay we show that cAMP response element modulator (CREM) binds to the miR-375 promoter 3-fold above background and we find that CREM represses transcription from the miR-375 promoter 1.8-fold. While investigating miR-375 target genes we discovered that several microRNA:mRNA target prediction algorithms listed human CREM as a target gene of miR-375. The predicted binding site is conserved in primates but not in other species. We found that indeed miR-375 binds to the predicted site on human CREM and represses translation of a green fluorescent protein reporter gene by 30%. These findings suggest a primate-specific double-negative feedback loop, a mechanism that would keep these important ß-cell regulators in check.

Drug screening and genome editing in human pancreatic cancer organoids identifies drug-gene interactions and candidates for off-label treatment.

Pancreatic cancer (PDAC) is a highly aggressive malignancy for which the identification of novel therapies is urgently needed. Here, we establish a human PDAC organoid biobank from 31 genetically distinct lines, covering a representative range of tumor subtypes, and demonstrate that these reflect the molecular and phenotypic heterogeneity of primary PDAC tissue. We use CRISPR-Cas9 genome editing and drug screening to characterize drug-gene interactions with ARID1A and BRCA2. We find that missense- but not frameshift mutations in the PDAC driver gene ARID1A are associated with increased sensitivity to the kinase inhibitors dasatinib (p < 0.0001) and VE-821 (p < 0.0001). We conduct an automated drug-repurposing screen with 1,172 FDA-approved compounds, identifying 26 compounds that effectively kill PDAC organoids, including 19 chemotherapy drugs currently approved for other cancer types. We validate the activity of these compounds in vitro and in vivo. The in vivo validated hits include emetine and ouabain, compounds which are approved for non-cancer indications and which perturb the ability of PDAC organoids to respond to hypoxia. Our study provides proof-of-concept for advancing precision oncology and identifying candidates for drug repurposing via genome editing and drug screening in tumor organoid biobanks.

APS/SPR Virtual Chat: race, racism, and child health equity in academic pediatrics.

IMPACT: Institutional racism exists within Academic Pediatrics within the United States, and it affects our work as researchers, clinicians, and educators. Confronting institutional racism is a challenging life-long struggle for people of all races, but it should be part of the professional mission of all who work in Pediatrics. Creating a path to health equity for children in the United States will involve failure. We should not be daunted by that prospect.

Sacral Neuromodulation with the InterStim System for Overactive Bladder: 3-Year Results from the French Prospective, Multicenter, Observational SOUNDS Study.

BACKGROUND: SOUNDS strengthens the evidence basis of sacral neuromodulation (SNM) for overactive bladder (OAB) through real-world data. OBJECTIVE: To analyze diary-based effectiveness, quality of life (QoL), disease severity, symptom bother, and safety data for SNM with the InterStim system up to 3 yr after implantation. DESIGN, SETTING, AND PARTICIPANTS: Twenty-five representative French sites enrolled 291 patients with OAB followed according to the local standard of care. Overall, 229 patients received a de novo or replacement InterStim implant and had four follow-up visits, two within the first yr and annually thereafter. A total of 190 patients completed the fourth follow-up visit after a mean of 33.7 ± 3.7 mo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The effectiveness outcomes measured were changes in daily voids and leaks and the therapy responder rates. Other outcomes included validated QoL data (Ditrovie and EuroQol 5-dimension 5-level questionnaires), disease severity (Urinary Symptom Profile [USP]), symptom bother rated using a numeric rating scale (NRS), and safety data. Follow-up data were compared to baseline results using the Wilcoxon signed-rank test. RESULTS AND LIMITATIONS: Average daily voids and leaks were significantly reduced at all time points up to 3 yr after implantation (p < 0.05) except for voids at 21 mo in the group receiving a replacement device. The therapeutic response for urinary urge incontinence at the fourth follow-up was 72% for the de novo group and 86% for the replacement group. Disease-specific QoL (Ditrovie), OAB-specific symptom severity (USP domain 2), and NRS-rated disease bother were significantly improved at all visits (p < 0.001). Device- or procedure-related adverse events occurred in 49% of patients, with 68% of the events classified as minor (Clavien-Dindo grade I or II). Surgical revisions were performed in 33% of patients, including permanent removal in 13%, over a mean exposure time of 44.4 ± 15.3 mo. CONCLUSIONS: This study confirms the safety and effectiveness of SNM for OAB and improvements in QoL and disease bother in real life. PATIENT SUMMARY: Our study in French patients with overactive bladder showed that disease symptoms and bother were significantly reduced and quality of life was significantly improved over a study duration of approximately 3 yr after implantation of a device to stimulate nerves that control the bladder. This trial is registered at ClinicalTrials.gov as NCT02186041.