Early Readmission and Revision After Total Joint Arthroplasty: An Analysis of Cause and Cost.

Background: Bundled payments for total joint arthroplasty (TJA) were instituted by the Centers for Medicare and Medicaid Services (CMS) to reimburse providers a lump sum for operative and 90-day postoperative costs. Gaining a better understanding of which TJA patients are at risk for early return to the operating room (OR) is critical in preoperative optimization of those with modifiable risks, which could improve bundled-payment performance. Purpose: We sought to identify the most common reason for readmissions, as well as patient characteristics and costs, associated with early return to the OR among TJA patients. Methods: This was a retrospective cohort study of Medicare patients who had undergone primary total hip or knee arthroplasty (THA or TKA) between 2013 and 2018 at a tertiary care hospital. We used the CMS research identifiable files database to identify the most common reasons for readmissions and revisions within 90 days of surgery. Total billing claims were used to determine the cost of early readmissions and revisions. Multivariate regression analysis was used to determine the characteristics associated with early readmission or revision. Results: Out of 20 166 primary TJA patients identified, we found 1349 readmissions (5.6%) and 163 (0.8%) revisions within 90 days of surgery. Dislocation was the most common indication for readmission, and periprosthetic joint infection was the most common indication for revision. Early return to the OR was associated with a mean $105,988 (standard deviation [SD] = $76,865) in CMS claims for the inpatient stay. Factors associated with a higher risk of early reoperation were female sex, THA, longer length of stay, and discharge to long-term care facility. Conclusions: This retrospective cohort study found that early return to the OR after TJA increased overall 90-day costs by 260%, suggesting that early reoperation might have a significant impact on bundled payments. Further study is warranted.

Let Kids Play: Using Virtual Reality as a Substitute for General Anesthesia for Minor Procedures in Pediatric Population.

BACKGROUND: In the pediatric population, virtual reality (VR) has been used as an adjunct to augment analgesia and reduce the need for opioids. In this study, we review our experience using VR in lieu of anesthesia or sedation to enable minor procedures in children. METHODS: A retrospective chart review study was performed on patients who presented to our institution from 2019 to 2022 for hormone implant placement, exchange, or removal with VR distraction. Demographic and procedure information was recorded. The primary outcome was successful procedure completion without requiring pharmacologic sedation or analgesia. RESULTS: A total of 111 patients underwent the following minor procedures with VR and without anesthesia or sedation. Fourteen patients had multiple encounters resulting in a total of 126 encounters. The median age was 11 [6] years. 43 patients were female, 23 were female to male, 6 were non-binary, 7 were male, and 32 were male to female. 58 % had private insurance. Most common diagnosis was precocious puberty (54 %) followed by gender dysphoria (46 %). Most common procedure was implant placement (72 %). 69 % of procedures were performed in the clinic and 31 % in the OR. All procedures were completed without requiring the administration of additional sedation or anesthesia. None of the patients required intravenous catheter placement for the procedure. No intra-procedural complications were recorded. CONCLUSION: VR is a feasible option that can spare children from sedation or general anesthesia for minor procedures. VR may enable minor procedures in children to be successfully performed in clinic setting.

How Much Protection Does a Collar Provide? Assessing Risk of Early Periprosthetic Femur Fractures Following Total Hip Arthroplasty in Elderly Patients.

BACKGROUND: Periprosthetic fractures (PPFs) account for approximately 25% of early revisions following total hip arthroplasty (THA). Cemented femoral fixation is associated with a lower-risk of PPF, and collared-cementless stems may reduce the risk as well. The objective of this study was to compare early-PPF rates between cemented, collared-cementless, and non-collared cementless stems in elderly patients. METHODS: A consecutieve-series of 11,522 primary THAs performed between 2016 and 2021 at our institution in patients >65 years of age was identified. Stem types used were categorized as cemented, collared-cementless, or non-collared cementless. Patients undergoing THA who had cemented-stems were older, more commonly women, and more likely to have a posterior-approach. To reduce confounding of patient characteristics, we matched patients in the 3 stem-categories according to age, sex, and body mass index. This generated 3-groups (cemented, collared-cementless, and non-collared cementless) consisting of 936 patients per group. The mean age of these 2,808 patients was 73 years, the mean body mass index was 27, and 67% were women. Logistic regressions were used to evaluate risk-factors for early-PPF. In the entire cohort of primary THA in elderly patients, there were 85 early PPFs (0.7%) over the study period. RESULTS: Non-collared cementless stems were associated with an increased risk of early PPF (OR: 3.11; P = .03) compared to collared-cementless stems. There were no early PPFs in the matched cemented cohort, 6 early PPFs in the matched collared-cementless cohort, and 16 early-PPFs in the matched non-collared cementless cohort (0% versus 0.64% versus 1.71%, P < .001). CONCLUSIONS: In this large-series of patients >65 years of age undergoing primary THA, cemented stem fixation had the lowest incidence of early PPF, but collared-cementless stems had a nearly 3-fold decrease in risk for early PPF compared to non-collared cementless stems.

Dislocation Following Anterior and Posterior Total Hip Arthroplasty in the Setting of Spinal Deformity and Stiffness: Evolving Trends Using a High-Risk Protocol at a Single Tertiary Center.

BACKGROUND: Patients who have spinal stiffness and deformity are at the highest risk for dislocation after total hip arthroplasty (THA). Previous reports of this cohort are limited to antero-lateral and postero-lateral (PL) approaches. We investigated the dislocation rate after direct anterior (DA) and PL approach THA with a contemporary high-risk protocol to optimize stability. METHODS: We investigated patients undergoing THA who had preoperative biplanar imaging from January-December 2019. Patients were identified using radiographic criteria of spinal-stiffness (<10-degree change in sacral slope from standing to seated) and deformity (flatback deformity with >10-degree difference in pelvic incidence and lumbar lordosis). There were 367 patients identified (181 DA, 186 PL). The primary outcome was dislocation rate at 2-years postoperatively. Risk-factors for dislocation were evaluated using logistic regressions (significance level of 0.05). RESULTS: There were 6 (1.6%) dislocations in the entire cohort, with low dislocation rates for both DA (0.6%) and PL-THA (2.7%). We observed increased utilization of dual mobility with larger outer head bearings (>38 mm) with PL-THA (34.4 versus 5.0%, P < .01) and conversely increased utilization of 32-mm femoral-heads with DA-THA (39.4 versus 7.0%, P < .001). Surgical approach (PL) was not a significant risk-factor for dislocation (odds ratio: 5.03, P = .15). Patients who had a history of lumbar-fusion had 8-times higher odds for dislocation (OR: 8.20, P = .020). CONCLUSIONS: To the best of our knowledge, this is the largest series to date evaluating DA and PL-THA in the hip-spine 2B-group. Our results demonstrate lower dislocation rate than expected with either surgical approach using a high-risk protocol.

Requerimientos para la producción e implementación de un Material Educativo Digital / Requirements for Producing and Implementing Digital Educational Materials

Introducción: La revolución digital ha llegado al campo educativo y exige que los entornos educativos digitales generen experiencias educativas contundentes. Para realizar este proceso, es fundamental diseñar y construir un material educativo digital (MED) ajustado a los lineamientos tecnológicos, técnicos y pedagógicos enmarcados en la neurobiología del aprendizaje (NA) del estudiante. Objetivo: Evaluar los elementos necesarios para la producción de un material educativo digital (MED) inédito, mediante su implementación en estudiantes. Métodos: Se realizó un análisis cuantitativo a través del Test de Wilcoxon SR con el software SPSS de IBM, y un análisis cualitativo con el software QDA Miner. Posteriormente, se triangularon los datos. Resultados: En el análisis cuantitativo se obtuvo una diferencia estadísticamente significativa entre el pretest y el postest (p < 0,001) y la mediana entre dicha diferencia de 22,6 por ciento. En el análisis cualitativo se definieron tres categorías: los comentarios positivos de la experiencia, las sugerencias de los estudiantes al proceso y las dificultades técnicas surgidas durante la implementación. Conclusiones: Son evidentes el interés, la motivación, el enganche y el disfrute de los estudiantes de una forma activa en el proceso de aprendizaje, que proporcionan un punto de partida para transformar las prácticas educativas con resultados significativos(AU)

Introduction: The digital revolution has reached the educational field and demands that digital educational environments generate powerful educational experiences. To carry out this process, it is essential to design and build a digital educational material adjusted to the technological, technical and pedagogical guidelines framed in the student's neurobiology of learning. Objective: To evaluate the necessary elements for the production of an unpublished digital educational material, through its implementation in students. Methods: A quantitative analysis was performed through the Wilcoxon SR test using the IBM SPSS software, together with a qualitative analysis using the QDA Miner software. Subsequently, the data were triangulated. Results: The quantitative analysis yielded a statistically significant difference between pretest and posttest (p < 0.001), as well as a median difference of 22.6 percent. The qualitative analysis permitted to define three categories: positive comments on the experience, the students' suggestions to the process, and technical difficulties encountered during the implementation. Conclusions: The students' active interest in, motivation for, engagement towards and enjoyment of the learning process are evident, facts that provide a starting point for transforming educational practices with significant outcomes(AU)

Percutaneous cervical sympathetic block to treat cerebral vasospasm and delayed cerebral ischemia: a review of the evidence.

Delayed cerebral ischemia (DCI) affects 30% of patients following aneurysmal subarachnoid hemorrhage (aSAH) and is a major driver of morbidity, mortality, and intensive care unit length of stay for these patients. DCI is strongly associated with cerebral arterial vasospasm, reduced cerebral blood flow and cerebral infarction. The current standard treatment with intravenous or intra-arterial calcium channel antagonist and balloon angioplasty or stent has limited efficacy. A simple treatment such as a cervical sympathetic block (CSB) may be an effective therapy but is not routinely performed to treat vasospasm/DCI. CSB consists of injecting local anesthetic at the level of the cervical sympathetic trunk, which temporarily blocks the innervation of the cerebral arteries to cause arterial vasodilatation. CSB is a local, minimally invasive, low cost and safe technique that can be performed at the bedside and may offer significant advantages as complementary treatment in combination with more conventional neurointerventional surgery interventions. We reviewed the literature that describes CSB for vasospasm/DCI prevention or treatment in humans after aSAH. The studies outlined in this review show promising results for a CSB as a treatment for vasospasm/DCI. Further research is required to standardize the technique, to explore how to integrate a CSB with conventional neurointerventional surgery treatments of vasospasm and DCI, and to study its long-term effect on neurological outcomes.

Reasons and Risk Factors for Failed Same-Day Discharge After Primary Total Knee Arthroplasty.

BACKGROUND: As ambulatory total knee arthroplasty (TKA) becomes increasingly common, unplanned admission after surgery presents a challenge for the health care system. Studies evaluating the reasons and risk factors for this occurrence are limited. We sought to evaluate the reasons for unplanned admission after surgery and identify risk factors associated with this occurrence. METHODS: Patients registered in an institutional ambulatory joint arthroplasty program who underwent a TKA from 2017-2020 were retrospectively reviewed. The criteria for enrollment include candidates for unilateral TKA between the ages of 18 and 70 years, with a body mass index (BMI) of less than 35, and appropriate social and material support at home. Patients who had certain comorbidities including coronary artery disease, valvular heart disease, and opioid dependence were not eligible. A total of 274 patients who underwent TKA with planned same-day discharge (SDD) were identified in the medical record and reviewed. In this cohort, 140 patients (51.1%) were discharged on the day of surgery and 134 patients (48.9%) required a minimum 1-night admission. Demographics, comorbidities, and perioperative data were collected. Factors associated with failed SDD were identified using multivariate logistic regression. RESULTS: The most common reasons for failed SDD were failure to meet ambulation goals (25%) and logistical issues related to a late-day case (19%). Risk factors for failed SDD include general anesthesia (odds ratio (OR) 12.60, P = .047), procedure start time after 11:00 am (OR 5.16, P < .001), highest postoperative pain score >8 (visual analogue scale, OR 5.78, P = .001). Willingness to accept a higher pain threshold before discharge (visual analogue scale 4 to 10) was associated with successful SDD (OR 3.0, P < .001). Age and American Society of Anesthesiologists (ASA) classification were not associated with failed SDD. CONCLUSIONS: The most common reasons for failed SDD were related to logistical issues and postoperative mobilization. Risk factors for failed SDD involve case timing and pain control. Modifiable perioperative factors may play an important role in successful SDD after TKA.

Ambulatory total hip arthroplasty: Causes for failure to launch and associated risk factors.

AIMS: The volume of ambulatory total hip arthroplasty (THA) procedures is increasing due to the emphasis on value-based care. The purpose of the study is to identify the causes for failed same-day discharge (SDD) and perioperative factors leading to failed SDD. METHODS: This retrospective cohort study followed pre-selected patients for SDD THA from 1 August 2018 to 31 December 2020. Inclusion criteria were patients undergoing unilateral THA with appropriate social support, age 18 to 75 years, and BMI < 37 kg/m2. Patients with opioid dependence, coronary artery disease, and valvular heart disease were excluded. Demographics, comorbidities, and perioperative data were collected from the electronic medical records. Possible risk factors for failed SDD were identified using multivariate logistic regression. RESULTS: In all, 278 patients were identified with a mean age of 57.1 years (SD 8.1) and a mean BMI of 27.3 kg/m2 (SD 4.5). A total of 96 patients failed SDD, with the most common reasons being failure to clear physical therapy (26%), dizziness (22%), and postoperative nausea and vomiting (11%). Risk factors associated with failed SDD included smokers (odds ratio (OR) 6.24; p = 0.009), a maximum postoperative pain score > 8 (OR 4.76; p = 0.004), and procedures starting after 11 am (OR 2.28; p = 0.015). A higher postoperative tolerable pain goal (numerical rating scale 4 to 10) was found to be associated with successful SDD (OR 2.7; p = 0.001). Age, BMI, surgical approach, American Society of Anesthesiologists grade, and anaesthesia type were not associated with failed SDD. CONCLUSION: SDD is a safe and viable option for pre-selected patients interested in rapid recovery THA. The most common causes for failure to launch were failing to clear physical thereapy and patient symptomatology. Risk factors associated with failed SSD highlight the importance of preoperative counselling regarding smoking cessation and postoperative pain to set reasonable expectations. Future interventions should aim to improve patient postoperative mobilization, pain control, and decrease symptomatology.Cite this article: Bone Jt Open 2022;3(9):684-691.

Cemented Femoral Fixation in a High-Risk Cohort Diminishes Risk of Early Postoperative Periprosthetic Fracture.

BACKGROUND: Early periprosthetic fractures (PPFx) following primary total hip arthroplasty (THA) create significant morbidity. Established risk factors for early PPFx include age, gender, body mass index, surgical approach, and implant fixation. We investigated the role of femoral fixation on early PPFx (<90 days postoperatively) in a high-risk cohort undergoing direct anterior approach (DAA) THA. METHODS: The final cohort comprised 344 consecutive patients (390 hips) with risk factors for PPFx (age >68 years and body mass index <25 kg/m2) who underwent primary DAA THA between May 4, 2009 and December 31, 2019 and had 90-day follow-up. Noncemented fixation was used in 229-hips, while cemented fixation was used in 161 hips. The primary outcome was early PPFx. Fisher's exact test was used for categorical variables, while t-tests were used to compare continuous variables. RESULTS: We observed 8 early PPFx (2.1%), all fractures occurring in the noncemented group. Baseline demographics were similar but not equal, with the cemented group being older (78.0 versus 76.3 years; P = .004) with a greater proportion of females (91.9% versus 69.4%; P < .001). The rate of early PPFx was significantly higher with noncemented fixation compared to cemented fixation (3.5% versus 0.0%; P = .023). A post hoc power analysis confirmed sufficient power (1-ß = 0.81). CONCLUSION: Although baseline risk factors for early PPFx are not easily modifiable, surgical factors can be modified. Cemented fixation has the potential to markedly reduce the risk of early PPFx in high-risk patients undergoing DAA THA.

Predicting Total Knee Arthroplasty Outpatient Discharge: Surgeons versus Insurance Companies.

BACKGROUND: Insurance companies are increasingly making unilateral determinations of admission status for primary total knee arthroplasty (TKA). These determinations may differ from those based on surgeon-derived criteria for outpatient knee replacement. The goal of this study is to determine if insurance company determinations of outpatient status are as reliable as surgeon-derived criteria in predicting outpatient discharge after TKA. METHODS: We retrospectively reviewed 709 patients who were preoperatively authorized for outpatient TKA. Patients were stratified into 2 groups: "outpatient per surgeon" (appropriate for outpatient surgery per institutional protocols) or "outpatient per insurance" (appropriate for inpatient surgery per institutional protocols but denied inpatient status by insurance). The primary endpoint of this study was the conversion rate of outpatient to inpatient stay. Univariate logistic regression was performed to compare the odds of conversion to inpatient stay between outpatient per surgeon and outpatient per insurance procedures and other covariates. RESULTS: The cohort included 434 outpatient per insurance (61.2%) and 275 outpatient per surgeon (38.8%) patients. Surgeons accurately predicted outpatients' discharge 92.0% of the time, while insurance companies did so 81.3% of time (P < .001). Outpatient per insurance procedures (odds ratio [OR] 2.20, P = .003) and body mass index >35 kg/m2 (OR 1.82, P = .026) had higher odds of being converted to inpatient. Males had higher odds (OR 1.52, P < .001) of being discharged as outpatient. CONCLUSION: Determining inpatient versus outpatient status is a complex decision involving both clinical and social factors. Surgeons accurately predicted outpatient discharge 92% of the time. Moreover, outpatient per insurance procedures were twice as likely to be converted to inpatient status. Therefore, insurance companies should leave deciding admission status up to both the patient and surgeon.

The Future is Non-cemented Total Knee Arthroplasty: Volume Trends at the Hospital for Special Surgery.

INTRODUCTION: The optimal fixation method for total knee arthroplasty (TKA) is still a debate. Cemented fixation has excellent long-term results and is the gold standard. However, longevity in the younger, heavier, and more active population is suboptimal. Cementless TKA offers the opportunity to gain biological fixation and overcome these shortcomings. METHODS: This is a retrospective review of all consecutive cementless TKA procedures performed at a single academic institution from 2016 until 2020. Demographics, aseptic revisions, and septic revisions were pulled from the electronic medical record. The number of yearly implanted cementless TKA prosthesis was determined to analyze utilization trends. RESULTS: Eight-hundred and two patients were identified with a mean age of 61.57 ± 7.78 years, and a mean of BMI 32.12 ± 5.98 kg/m2. The mean time to revision was 12.31 ± 13.91 months. There were four septic failures and nine aseptic failures during the study period. Of these nine aseptic failures only five were due to mechanical loosening. There was a yearly linear increase in the use of cementless fixation. CONCLUSION: Cementless fixation is here to stay, and its use will continue to increase. Early and mid-term outcomes have been excellent thus far. Changing clinical practice takes time but we have already seen this transition take place in total hip arthroplasty. As technology and design continue to evolve, we believe it is a possibility.

Small surgeries, big smiles: using virtual reality to reduce the need for sedation or general anesthesia during minor surgical procedures.

PURPOSE: Children often require anesthesia for simple diagnostic and therapeutic procedures. The aim of this study was to evaluate the feasibility of using virtual reality (VR) to reduce sedation in children undergoing minor surgical procedures. METHOD: In this prospective, non-randomized clinical trial, pediatric patients at a free-standing children's hospital undergoing hormone implant placement, removal, or exchange were recruited to use VR and local anesthesia instead of procedural sedation or general anesthesia (GA). Patients were enrolled between November 2017 and March 2020, and were compared to historic controls who underwent similar procedures without VR between April 2016 and February 2020. Primary outcome measure was successful procedure completion without sedation or GA. Secondary measures included assessments of pain, fear and anxiety, patient compliance, procedural and recovery times. RESULTS: Twenty-eight patients underwent 29 procedures with VR. Hormone implants (72%), removals (7%), or exchanges (21%) were completed without GA, sedation or IV placement. Procedure lengths and pain scores were similar between VR patients and historic controls, but recovery times were significantly shorter in VR patients (18 vs 65 min, p < 0.001). Participant satisfaction scores were high, with 95% recommending VR to others. CONCLUSIONS: VR is a feasible alternative to sedation or GA for select pediatric patients undergoing minor surgical procedures.

Exosome loaded immunomodulatory biomaterials alleviate local immune response in immunocompetent diabetic mice post islet xenotransplantation.

Foreign body response (FBR) to biomaterials compromises the function of implants and leads to medical complications. Here, we report a hybrid alginate microcapsule (AlgXO) that attenuated the immune response after implantation, through releasing exosomes derived from human Umbilical Cord Mesenchymal Stem Cells (XOs). Upon release, XOs suppress the local immune microenvironment, where xenotransplantation of rat islets encapsulated in AlgXO led to >170 days euglycemia in immunocompetent mouse model of Type 1 Diabetes. In vitro analyses revealed that XOs suppressed the proliferation of CD3/CD28 activated splenocytes and CD3+ T cells. Comparing suppressive potency of XOs in purified CD3+ T cells versus splenocytes, we found XOs more profoundly suppressed T cells in the splenocytes co-culture, where a heterogenous cell population is present. XOs also suppressed CD3/CD28 activated human peripheral blood mononuclear cells (PBMCs) and reduced their cytokine secretion including IL-2, IL-6, IL-12p70, IL-22, and TNFα. We further demonstrate that XOs mechanism of action is likely mediated via myeloid cells and XOs suppress both murine and human macrophages partly by interfering with NFκB pathway. We propose that through controlled release of XOs, AlgXO provide a promising new platform that could alleviate the local immune response to implantable biomaterials.

Using Augmented Reality to Reduce Fear and Promote Cooperation During Pediatric Otolaryngologic Procedures.

This case series examines interactive AR during minor otolaryngologic procedures. Although VR has been successfully used for pediatric vascular access, removing children from comforting people in the real world has resulted in patient anxiety. AR offers a potential advantage, utilizing distracting holographic images when patients maintain eye contact with parents. The primary objective was to determine the effect of AR on fear during pediatric otolaryngologic procedures. Secondary objectives included evaluating pain; procedure compliance; and patient, parent and physician attitudes toward AR, as well as assessing the feasibility of adding AR to a busy outpatient otolaryngologic clinic. Laryngoscope, 131:E1342-E1344, 2021.

A retrospective cohort study of predictors and interventions that influence cooperation with mask induction in children.

BACKGROUND: Uncooperative pediatric mask induction is linked to perioperative anxiety. Although some risk factors for uncooperative inductions have been reported, there are no large cohort studies that identify intrinsic patient characteristics associated with cooperation. AIM: The primary aim was to identify patient characteristics associated with cooperative mask inductions. The secondary aim was to determine whether preoperative interventions were associated with increased cooperation. METHODS: This retrospective cohort study included patients 2-11 years old and ASA class I-IV who underwent mask induction. Our primary outcome of interest was cooperation with mask induction, which was correlated against the Induction Compliance Checklist. The variables analyzed for association with cooperation were age, sex, ASA class, class of surgery, preferred language, and race. Interventions examined for association with induction cooperation included premedication with midazolam, exposure to distraction technology, parental presence, and the presence of a Child Life Specialist. Multivariate mixed-effects logistic regression was used to assess the relationship between patient characteristics and cooperation. A separate multivariate mixed-effects logistic regression was used to examine the association between preoperative interventions and cooperation. RESULTS: 9692 patients underwent 23 474 procedures during the study period. 3372 patients undergoing 5980 procedures met inclusion criteria. The only patient characteristic associated with increased cooperation was age (OR 1.20, p-value 0.03). Involvement of Child Life Specialists was associated with increased cooperation (OR 4.44, p-value = 0.048) while parental/guardian presence was associated with decreased cooperation (OR 0.38, p-value = 0.002). CONCLUSION: In this cohort, increasing age was the only patient characteristic found to be associated with increased cooperation with mask induction. Preoperative intervention by a Child Life Specialists was the sole intervention associated with improved cooperation.

Controlled Release of Stem Cell Secretome Attenuates Inflammatory Response against Implanted Biomaterials.

Inflammatory response against implanted biomaterials impairs their functional integration and induces medical complications in the host's body. To suppress such immune responses, one approach is the administration of multiple drugs to halt inflammatory pathways. This challenges patient's adherence and can cause additional complications such as infection. Alternatively, biologics that regulate multiple inflammatory pathways are attractive agents in addressing the implants immune complications. Secretome of mesenchymal stromal cells (MSCs) is a multipotent biologic, regulating the homeostasis of lymphocytes and leukocytes. Here, it is reported that alginate microcapsules loaded with processed conditioned media (pCM-Alg) reduces the infiltration and/or expression of CD68+ macrophages likely through the controlled release of pCM. In vitro cultures revealed that alginate can dose dependently induce macrophages to secrete TNFα, IL-6, IL-1ß, and GM-CSF. Addition of pCM to the cultures attenuates the secretion of TNFα (p = 0.023) and IL-6 (p < 0.0001) by alginate or lipopolysaccharide (LPS) stimulations. Mechanistically, pCM suppressed the NfκB pathway activation of macrophages in response to LPS (p < 0.0001) in vitro and cathepsin activity (p = 0.005) in response to alginate in vivo. These observations suggest the efficacy of using MSC-derived secretome to prevent or delay the host rejection of implants.

Impact of Audiovisual-Assisted Therapeutic Ambience in Radiation Therapy (AVATAR) on Anesthesia Use, Payer Charges, and Treatment Time in Pediatric Patients.

PURPOSE: Pediatric radiation therapy (RT) requires optimal immobilization that often necessitates daily anesthesia. To decrease anesthesia use, we implemented a novel audiovisual-assisted therapeutic ambience in RT (AVATAR) system that projects video onto a radiolucent screen within the child's line of vision to provide attentional diversion. We investigated its reduction on anesthesia use, payer charges, and treatment time, in addition to its impact on radiation delivery. METHODS AND MATERIALS: A 6-year retrospective analysis was performed among children undergoing RT (n = 224) 3 years before and 3 years after the introduction of AVATAR. The frequency of anesthesia use before and after AVATAR implementation, in addition to RT treatment times, were compared. The number of spared anesthesia treatments allowed for a charge to payer analysis. To document the lack of surface dose perturbation by AVATAR, a phantom craniospinal treatment course was delivered both with and without AVATAR. Additionally, an ion chamber course was delivered to document changes to the dose at depth. RESULTS: More children were able to avoid anesthesia use entirely in the post-AVATAR cohort compared with the pre-AVATAR cohort (73.2% vs 63.4%; P = .03), and fewer required anesthesia for each treatment (18.8% vs 33%; P = .03). AVATAR introduction reduced anesthesia use for all ages studied. Treatment time per session was reduced by 38% using AVATAR compared with anesthesia. There were 326 fewer anesthesia sessions delivered over 3 years after AVATAR was introduced, with an estimated savings of >$500,000. Optically stimulated luminescent dosimeters revealed a small increase in dose of 0.8% to 9.5% with AVATAR, whereas the use of a thermomolded face mask increased skin dose by as much as 58%. CONCLUSIONS: AVATAR introduction decreased anesthesia use in children undergoing RT. More children avoided anesthesia entirely, and fewer needed anesthesia for every treatment, resulting in a reduction in treatment time and savings of nearly $550,000 in approximately 3 years, with minimal perturbation of RT dose delivery.

Two novel variants in the ATM gene causing ataxia-telangiectasia, including a duplication of 90 kb: Utility of targeted next-generation sequencing in detection of copy number variation.

Ataxia-telangiectasia (A-T) is a rare autosomal recessive neurodegenerative disorder characterized by progressive cerebellar ataxia, ocular apraxia, immunodeficiency, telangiectasia, elevated serum α-fetoprotein concentration, radiosensitivity and cancer predisposition. Classical A-T is caused by biallelic variants on ATM (ataxia telangiectasia mutated) gene, leading to a loss of function of the protein kinase ATM, involved in DNA damage repair. Atypical presentations can be found in A-T-like disease or in Nijmegen breakage syndrome, caused by deficiency of mre11 or nibrin proteins, respectively. In this report, we present the genetic characterization of a 4-year-old female with clinical diagnosis of A-T. Next-generation sequencing (NGS) revealed two novel heterozygous mutations in the ATM gene: a single-nucleotide variant (SNV) at exon 47 (NM_000051.3:c.6899G > C; p.Trp2300Ser) and ∼90 kb genomic duplication spanning exons 17-61, NG_009830.1:g.(41245_49339)_(137044_147250)dup. These findings were validated by Sanger sequencing and MLPA (multiplex ligation-dependent probe amplification) analysis respectively. Familial segregation study confirmed that the two variants are inherited, and the infant is a compound heterozygote. Thus, our study expands the spectrum of ATM pathogenic variants and demonstrates the utility of targeted NGS in the detection of copy number variation.